• Furthermore, the expression of the genes known to govern insulin expression including Pdx1 and Ngn3 was markedly induced by laminin 411, which suggests that Pdx 1 and Ngn 3 signaling pathways are involved in laminin 411 induced-insulin expression machinery. (biomedcentral.com)
  • Our results demonstrate that laminin 411 acts as a potent differentiation inducer of IPCs from UC-MSCs via the Pdx1 and Ngn3 signaling pathways. (biomedcentral.com)
  • Some of these pancreatic progenitors are converted into endocrine precursor cells, which then express the protein Ngn3 from embryonic day 11.5 to 18. (livingwithdiabetes.info)
  • These Ngn3 -expressing precursors ultimately give rise to all of the islet endocrine cells. (livingwithdiabetes.info)
  • Although endocrine pancreas progenitor cells have been isolated from mouse pancreata on the basis of Ngn3 expression, human endocrine progenitors have not been isolated yet. (crick.ac.uk)
  • As substantial differences exist between human and murine pancreas biology, we investigated whether it is possible to isolate pancreatic endocrine progenitors from differentiating hESC cultures by lineage tracing of NGN3. (crick.ac.uk)
  • We targeted the 3' end of NGN3 using zinc finger nuclease-mediated homologous recombination to allow selection of NGN3eGFP(+) cells without disrupting the coding sequence of the gene. (crick.ac.uk)
  • This confirms that NGN3(+) cells represent pancreatic endocrine progenitors in humans. (crick.ac.uk)
  • Nevertheless, Ngn3- and NeuroD-induced delamination of endodermal cells was insensitive to activated Notch under these conditions. (biomedcentral.com)
  • Our results also demonstrate that Notch can repress Ngn3 and NeuroD protein function and stimulate progenitor proliferation. (biomedcentral.com)
  • To determine whether Notch in fact does act in Ngn3-expressing cells in vivo will require further studies relying on conditional mutagenesis. (biomedcentral.com)
  • At this stage there is an increase in the numbers of Ngn3 positive cells in Dll1 and RBP-Jκ mutants, and at E10.5 an increase in endocrine cells. (biomedcentral.com)
  • Ngn3 expression was not analyzed in Hes1 mutants but these had increased numbers of glucagon-producing cells at E9.5. (biomedcentral.com)
  • Bi- or tri-cistronic constructs were generated in hybrid adenovirus/adeno-associated virus (Ad/AAV) vectors containing neurogenin 3 (NGN3), BETA2 (NeuroD), and RIPE3b1 (MafA), each of which plays a role in islet cell differentiation. (elsevierpure.com)
  • OGT ablation in endocrine progenitors (Ngn3 + , OGTKO Endo ) resulted in normal pancreas mass but reduced β-cell mass and diabetes early in life, strongly revealing the temporal and importance of OGT for β-cell development. (diabetesjournals.org)
  • Ectopic expression of vector-delivered transcription factors (particularly the triumvirate of Pdx1, Ngn3 and MafA) induces reprogramming through broad transcriptional remodelling. (silverchair.com)
  • Addition of retinoic acid (RA), Noggin and Cyclopamine promoted pancreatic differentiation as indicated by the expression of the early pancreatic progenitor markers ISL1, NGN3 and PDX1. (ox.ac.uk)
  • 1996). Development of gut enteroendocrine and pancreatic endocrine cells also depends on common critical factors, such as Ngn3 (also known as Neurog3) (Gu et al. (diabetesresearchconnection.org)
  • 2002). Recent studies showed that intestinal cells could be converted into insulin+ cells with either endocrine-specific deletion of FoxO1 or ubiquitous expression of NPM reprogramming factors (Ngn3, Pdx1, and Mafa) (Bouchi et al. (diabetesresearchconnection.org)
  • Human embryonic stem cells (hESC) may one day be used as a source of pancreatic progenitor cells and/or b cells for transplantation into patients with type I diabetes mellitus. (rotrf.org)
  • Pancreatic endocrine progenitors obtained from human embryonic stem cells (hESCs) represent a promising source to develop cell-based therapies for diabetes. (crick.ac.uk)
  • Resveratrol ameliorates the maturation process of β-cell-like cells obtained from an optimized differentiation protocol of human embryonic stem cells. (ox.ac.uk)
  • Human embryonic stem cells (hESCs) retain the extraordinary capacity to differentiate into different cell types of an adult organism, including pancreatic β-cells. (ox.ac.uk)
  • The long term goal of our research is to understand the biochemical processes that regulate differentiation of human embryonic stem cells (hESCs) into pancreatic progenitor cells, and ultimately, glucose-responsive, insulin producing (beta) β cells. (ca.gov)
  • These regenerative technologies include directed differentiation of embryonic stem cells and direct conversion from non-β cells such as liver cells, acinar cells, and others (Hebrok, 2012, Johannesson et al. (diabetesresearchconnection.org)
  • Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas. (wikipedia.org)
  • Mnx1 expression has been shown to be important for the development of dorsal Pdx1, hence acting as a necessary transcription factor for the specification of foregut endoderm into Pdx1 expressing pancreatic progenitors. (wikipedia.org)
  • It is important to note here that the developing dorsal and ventral buds are characterized as endoderm, and it isn't until the expression of Pdx1 (specification of endoderm to a stem cell multipotent state) that the endoderm to pancreatic progenitor transition occurs. (wikipedia.org)
  • We have recently developed a novel culture protocol based in part on known signaling events in pancreas specification to promote hESC to differentiate into endoderm and proliferative PDX1+ pancreatic epithelia. (rotrf.org)
  • Here, we employed a human pancreatic differentiation platform complemented with an shRNA screen in human pluripotent stem cells (PSCs) to identify potential drivers of early endoderm and pancreatic development. (mdpi.com)
  • In conclusion, our strategy allows the efficient differentiation of hESCs into pancreatic endoderm capable of generating β-cell-like cells and demonstrates that RSV improves the maturation process. (ox.ac.uk)
  • Conversely, miR-122 is the most highly expressed miRNA in liver, which arises in the region of endoderm that is closest to the pancreatic buds. (ca.gov)
  • We firstly show that the endoderm, by expressing the fgf24 gene at early stages, triggers the patterning of the pancreatic lateral plate mesoderm. (biologists.com)
  • ventral pancreatic precursor 1 ( vpp1 ) is a marker gene that is differentially expressed in a cell population within the dorsal endoderm in a pattern partially overlapping with that of hematopoietically expressed homeobox ( hhex ) during gastrulation. (xenbase.org)
  • vpp1 and hhex display partially overlapping expression in gas - trulating dorsal endoderm and later demarcate ventral pancreatic buds and liver anlagen, respectively. (xenbase.org)
  • L) Statistic analysis of phospho- histone H3-positive cells on the whole surface of bisected vegetal endoderm , as demarcated by the red dashed lines in J and K. As the distribution of phospho-histone H3-positive cells across the whole vegetal endoderm sur - face did not show obvious bias, for simplicity, we counted the whole area rather than only putative vpp1 -positive area. (xenbase.org)
  • Differentiate human pluripotent stem cells (hPSCs) to cells of the endoderm lineage with our specialized cell culture media. (stemcell.com)
  • See More Use our definitive endoderm (DE) differentiation kit to obtain functional DE cells that are capable of downstream differentiation to hepatic, intestinal, pancreatic and pulmonary cells. (stemcell.com)
  • In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. (patsnap.com)
  • Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. (patsnap.com)
  • Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. (patsnap.com)
  • Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed. (patsnap.com)
  • In some cases, painless jaundice may be a symptom of early pancreatic cancer that can be cured with surgery. (medicinenet.com)
  • Mcam It is usually worth noting that PDX1 is usually widely expressed in early pancreatic progenitors, but in the adult pancreas its manifestation is usually largely restricted to insulin-producing cells. (technuc.com)
  • They give rise to both the endocrine and exocrine cells. (wikipedia.org)
  • Exocrine cells constitute the acinar cells and the ductal cells. (wikipedia.org)
  • The fused and developed pancreas consists of pancreatic enzyme secreting cells (exocrine cells), digestive enzyme transporting cells (ductal cells) and hormone producing cells (endocrine cells). (wikipedia.org)
  • This transcription factor has been shown to give rise to the multipotent stem cell lineages contributing to the endocrine, exocrine and ductal cells of the pancreas. (wikipedia.org)
  • Notch signaling has been shown to regulate the number of exocrine and endocrine cells in the pancreas, but not without the presence of Pdx1. (wikipedia.org)
  • Isolated NGN3eGFP(+) cells express PDX1, NKX6.1, and chromogranin A and differentiate in vivo toward insulin, glucagon, and somatostatin single hormone-expressing cells but not to ductal or exocrine pancreatic cells or other endodermal, mesodermal, or ectodermal lineages. (crick.ac.uk)
  • Studies have also identified other contender genes and genomic disruptions in human pancreatic exocrine tumors classified patients into different subclasses based on tumor histotypes and cancer-specific chromosomal rearrangements ( 7 - 9 ). (amegroups.org)
  • The pancreas is an organ containing both exocrine and endocrine cell populations. (biomedcentral.com)
  • Lineage tracing studies have revealed that both endocrine and exocrine cells are derived from Pdx1 -expressing progenitors [ 1 - 3 ]. (biomedcentral.com)
  • Genetic analysis has recently identified four pancreatic cancer subtypes -- squamous, pancreatic progenitor, aberrantly differentiated endocrine exocrine (ADEX), and immunogenic. (medicinenet.com)
  • Phylo-epigenetic and cell-type signature features derived from alpha, beta, acinar, and ductal adult cells suggest an exocrine cell of origin for PanNECs, thus separating them in cell lineage from other PanNENs of endocrine origin. (biomedcentral.com)
  • SOX9, a downstream target of NOTCH, is required for the establishment of cell fates of endocrine and exocrine cells [ 34 , 35 ]. (biomedcentral.com)
  • Pancreatic stellate cells (PSCs) are resident cells of the pancreas, found in both the exocrine and endocrine parts of the gland. (pancreapedia.org)
  • These organoids harbor a subpopulation of ALDH hi cells that display proliferative capacity and can differentiate to an endocrine fate. (prinsesmaximacentrum.nl)
  • Human pluripotent stem cells, with their ability to proliferate indefinitely and to differentiate into virtually all cell types of the human body, provide a novel resource to study human development and to implement relevant disease models. (mdpi.com)
  • Transcription factors, such as PDX-1, that normally mediate pancreatic development are capable of inducing hepatic progenitor cells to differentiate into cells with pancreatic islet characteristics. (elsevierpure.com)
  • Tracing these cells reveals that they are able to differentiate into other ductal cells and into Insulin-expressing cells in normal - non-diabetic - animals. (refine.bio)
  • hESCs, which can undergo unlimited self-renewal and differentiate into all cell types in the body, have the potential to become an unlimited source of pancreatic β cells, however, significant challenges have hindered clinic development of this promising hESC based therapy. (ca.gov)
  • To directly differentiate to pancreatic cells, use our pancreatic progenitor kit to generate functional PDX1 + /NKX6.1 + cells that can be matured into insulin-producing beta cells. (stemcell.com)
  • To identify the pancreatic cells able to give rise to new beta cells in zebrafish, we generated new transgenic lines allowing the tracing of multipotent pancreatic progenitors and endocrine precursors. (refine.bio)
  • Conclusions: We have shown that, in the zebrafish embryo, nkx6.1+ cells are bona fide multipotent pancreatic progenitors, while ascl1b+ cells represent committed endocrine precursors. (refine.bio)
  • We have made a cell line that reports the expression of PDX1, a marker for both pancreatic precursors and for mature beta cells, in order to select and purify the target cells in late differentiation. (ca.gov)
  • While SOX9 is absent in committed endocrine precursors, it is an important player in pancreatic ductal and centro-acinar cell development but not in adult acinar cells [ 36 , 37 ]. (biomedcentral.com)
  • Homeoprotein hhex -induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos. (xenbase.org)
  • These endocrine cells develop in discrete areas within the pancreas known as the islets. (wikipedia.org)
  • The development of beta cells precedes that of the development of other endocrine cells in the islets. (wikipedia.org)
  • In this project, we will test the hypothesis that human PDX1+ pancreatic progenitor cells stimulate a less vigorous immune response than normal adult islets by studying the adaptive immune responses to such cells in humanized mice. (rotrf.org)
  • In aim 3, we will examine whether progenitor cells can support the survival and function of a subtherapeutic mass of transplanted adult islets. (rotrf.org)
  • CONCLUSIONS/INTERPRETATION: Novel time-resolved analysis with Gcg-Timer reporter mice uncovered spatiotemporal features of alpha cell neogenesis that will enhance our understanding of cellular identity and plasticity within the islets. (bvsalud.org)
  • Global gene expression analysis of isolated islets indicated that the genes related to regulation of cell population proliferation and negative regulation of cell death were enriched by Imeg + Met treatment in db/db islets. (bvsalud.org)
  • However, the extent of autophagic flux in pancreatic islets induced in various physiological settings remains unclear. (bvsalud.org)
  • Islets were isolated from porcine pancreases and enzymatically digested to dissociate the component cells. (vt.edu)
  • Other labs have shown that miR-375 is also expressed in pancreatic during development, and specifically in beta cells in mature islets, where it regulates insulin secretion. (ca.gov)
  • PSCs are also found around small pancreatic ducts (5, 11), pancreatic islets (163) and blood vessels. (pancreapedia.org)
  • It has been seen in the developing embryo at stages E9.0 to E9.5 that there are a cluster of cells which give rise to the pancreas. (wikipedia.org)
  • Later these cells are shown to originate from the dorsal bud of the developing pancreas. (wikipedia.org)
  • Pdx1 expression is empirical to drive the developing pancreas after the bud stage where two buds (dorsal and lateral) of the immature pancreas develop. (wikipedia.org)
  • These cells have been shown to have 28 genes regulating the cell cycle to be upregulated, showing that they are proliferative cells having the ability to replace and give rise to multiple cell populations in the pancreas. (wikipedia.org)
  • Pancreatic progenitors have been shown to arise from the early expression of the gene Mnx1/Hlxb1 (Motor Neuron and pancreas homobox 1). (wikipedia.org)
  • Diabetes occurs due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced. (livingwithdiabetes.info)
  • Essentially, the genetic blueprint for building a pancreas is present in every single cell in the body, from the womb through adulthood, as is the blueprint for every organ and structure of your body. (livingwithdiabetes.info)
  • In addition, this hESC reporter line constitutes a unique tool that may aid in gaining insight into the developmental mechanisms underlying fate choices in human pancreas and in developing cell-based therapies. (crick.ac.uk)
  • Endocrine cells begin to appear soon after the first morphological signs of pancreas formation which occurs approximately at the 25-somite stage in the mouse and chicken [ 7 ]. (biomedcentral.com)
  • Several studies have demonstrated that Notch signaling is involved in the development of endocrine cells in the pancreas. (biomedcentral.com)
  • In this study, we tested the hypothesis that OGT is required for pancreas and β-cell development by deleting OGT in pancreatic (Pdx1Cre, OGTKO Panc ) or endocrine (Ngn3Cre, OGTKO Endo ) progenitors. (diabetesjournals.org)
  • We show that mice lacking OGT in pancreatic progenitors (Pdx1 + , OGTKO Panc ) show near pancreas agenesis and loss of β-cell mass at birth. (diabetesjournals.org)
  • These data highlight the novel role O-GlcNAc-modifications in pancreas and β-cell development and provide a new model to characterize the developmental defects associated with pancreatic agenesis. (diabetesjournals.org)
  • Cancer that starts in the pancreas is called pancreatic cancer. (medicinenet.com)
  • We believe that the results from this project have the potential to create a paradigm shift in understanding the cellular ontogeny of the pancreas and help identify which cell types can be used for transplantation therapy in T1D. (ca.gov)
  • In contrast, a populace of nonislet PDX1+ cells from the adult pancreas was found to have heightened sensitivity to Kras activation in normal noninflammatory conditions, and was proposed to represent the cell of source of PDAC (4). (technuc.com)
  • These cells reportedly reside in the ductal and centroacinar storage compartments (29, 43), and make up 1% of the adult pancreas (44). (technuc.com)
  • These data are consistent with the hypothesis that the adult pancreas harbors a dormant progenitor cell populace that is usually activated under conditions of oncogenic activation and is usually capable of initiating malignancy (4). (technuc.com)
  • DNA alterations and immunohistochemistry of cell-type markers PDX1, ARX, and SOX9 were utilized to further characterize PanNECs and their cell of origin in the pancreas. (biomedcentral.com)
  • PDACs have been shown to originate from normal ductal or acinar cells [ 20 , 21 ], while G1 and G2 PanNETs have been shown to originate from endocrine cells of the pancreas [ 22 , 23 , 24 ]. (biomedcentral.com)
  • These observations suggest that, beyond its role in liver development, hhex controls specification of a vpp1 -positive endodermal cell population during gastrulation that is required for the formation of the ventral pancreas . (xenbase.org)
  • Over the two decades since these cells were first isolated and cultured from rodent and human pancreas, research in this area has progressed at a rapid rate. (pancreapedia.org)
  • An improved understanding of PSC biology and of the interactions of PSCs with other pancreatic cells provides a strong platform for the development of novel therapeutic approaches for notoriously hard to treat diseases of the pancreas such as chronic pancreatitis and pancreatic cancer. (pancreapedia.org)
  • Pancreatic fibrosis is a well-recognized histopathological feature of two major diseases of the pancreas - chronic pancreatitis and pancreatic cancer. (pancreapedia.org)
  • In a healthy pancreas, PSCs make up 4-7% (5) of the total parenchyma and are located around the basolateral aspects of the acinar cells ( Figure 1A ). (pancreapedia.org)
  • Results: Using novel bacterial artificial chromosome transgenic nkx6.1 and ascl1b reporter lines, we established that nkx6.1-positive cells give rise to all the pancreatic cell types and ascl1b-positive cells give rise to all the endocrine cell types in the zebrafish embryo. (refine.bio)
  • These two genes are initially co-expressed in the pancreatic primordium and their domains segregate, not as a result of mutual repression, but through the opposite effects of Notch signaling, maintaining nkx6.1 expression while repressing ascl1b in progenitors. (refine.bio)
  • In adult zebrafish, nkx6.1 expression persists exclusively in the ductal tree at the tip of which its expression coincides with Notch active signaling in centroacinar/terminal end duct cells. (refine.bio)
  • This capacity of ductal cells to generate endocrine cells is supported by the detection of ascl1b in the nkx6.1:GFP ductal cell transcriptome. (refine.bio)
  • In contrast to mouse, pancreatic progenitor markers nkx6.1 and pdx1 continue to be expressed in adult ductal cells, a subset of which we show are still able to proliferate and undergo ductal and endocrine differentiation, providing the first robust evidence of the existence of pancreatic progenitor/stem cells in adult zebrafish. (refine.bio)
  • Our findings support the hypothesis that nkx6.1+ pancreatic progenitors contribute to beta cell regeneration. (refine.bio)
  • Moreover, although NPM factors induce insulin+ cells in the intestine, the induced cells appear to lack certain important β cell genes such as Nkx6.1 and exhibit reduced glucose responsiveness compared with pancreatic β cells (Chen et al. (diabetesresearchconnection.org)
  • The differential of pancreatic progenitors from hepatic progenitors is also notable, as Hhex1 (Hematopoietically expressed homeobox gene) is responsible for the origination of pancreatic progenitor cells. (wikipedia.org)
  • We hypothesized that simultaneous expression of multiple transcription factors involved in islet development might enhance the differentiation of hepatic progenitor cells. (elsevierpure.com)
  • Administration of the Ad/AAV hybrid vectors to streptozotocin-induced diabetic mice reversed hyperglycemia, consistent the differentiation of functional hepatic insulin-secreting cells. (elsevierpure.com)
  • These results indicate that Ad/AAV hybrid vectors can be used to administer combinations of factors that induce islet cell differentiation in hepatic progenitor cells. (elsevierpure.com)
  • However, lineage tracing studies with hepatic stellate cells (counterparts of PSCs in the liver) have confirmed a mesenchymal origin for these cells (9). (pancreapedia.org)
  • Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. (prinsesmaximacentrum.nl)
  • We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. (prinsesmaximacentrum.nl)
  • In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. (prinsesmaximacentrum.nl)
  • The central hypothesis driving the research is that miRNAs are essential regulators of endocrine cell development. (ca.gov)
  • Laminin 411 markedly induced the expression of the genes Foxa2 and Sox17 , markers for pancreatic precursor cells, efficiently induced IPC differentiation from MSCs, and up-regulated insulin expression at both mRNA and protein levels. (biomedcentral.com)
  • Here, our objective is to study how the human adaptive immune system recognizes and responds in vivo to an enriched, non-tumorforming population of hESC-derived pancreatic precursor cells, which express the homeodomain protein PDX1. (rotrf.org)
  • Specifically, the objectives of this CIRM grant are to elucidate the role miRNAs play in the development of hESC into cells of endocrine lineage and to provide crucial details on the molecular architecture of endocrine precursor populations, lineage specification, and β-cell maturation. (ca.gov)
  • Ectopic expression of a critical dose of hhex led to a greatly enlarged vpp1 -positive domain and, subsequently, to the formation of giant ventral pancreata, putatively by conversion of intestinal to ventral pancreatic precursor cells. (xenbase.org)
  • Of main importance, a phenotypic switch transforming adult pancreatic acinar cells (the most numerous pancreatic cell type) to duct-like cells can lead to pancreatic intraepithelial neoplasia (PanIN) and eventually to PDAC, but only in conjunction with chemically induced pancreatitis (3, 4, 39, 42). (technuc.com)
  • These genes regulates the expression of Mnx1 in the ventral bud, leading to the developmental specification of the pancreatic progenitor cells expressing Pdx1. (wikipedia.org)
  • They ground up some of the pancreatic tissue from the mice and used RNA sequencing to determine which genes were being expressed. (livingwithdiabetes.info)
  • In this study, we cultured islet-derived cells in vitro and examined the expression of β-cell genes during the proliferation. (vt.edu)
  • The islet-derived cells also expressed other pancreatic genes such as Pdx1, NeuroD, glucagon, and somatostatin. (vt.edu)
  • Taken together, these results indicate that pancreatic islet-derived cells, proliferated in vitro, retained the expression capacity for key pancreatic genes, thus suggesting that the cells may be redifferentiated into insulin-secreting β-like cells. (vt.edu)
  • and and and and and and Fig. S7 and and and W ) Phenotypic conversion of SCA1+ KrasG12D p53KO clonal cell lines transduced with the indicated genes comparative to vector-transduced controls. (technuc.com)
  • This work validates the use of blastocyst complementation as a tool to create novel insight into the function of developmental genes and highlights blastocyst complementation as a potential platform for generating chimeric inner ear cell types that can be transplanted into damaged inner ears to improve hearing. (biomedcentral.com)
  • This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
  • Genetic lineage tracing experiments have been performed by various research groups to show that the cell clusters originating from the developing foregut express a transcription factor called PDX1 (Pancreatic and duodenal homeobox 1). (wikipedia.org)
  • Mapping developmental expression of miRNAs during transition from pluripotency to pancreatic progenitors will help clarify the mechanisms underlying lineage specification and ultimately enhance differentiation protocols. (ca.gov)
  • BC is a technique in which deletion of a key gene for the development of a specific lineage creates a vacant niche (organogenesis-disabled phenotype) that can be complemented by the progeny of wild type pluripotent stem cells injected into embryos at the blastocyst stage of development. (biomedcentral.com)
  • To allow a biophysical characterization in vitro, we expressed the human full-length GLP-1R within the cytosol of Escherichia coli as inclusion our bodies. (ncbcs.org)
  • In vitro culture experiments confirmed the protective effects of Imeg + Met against ß-cell apoptosis. (bvsalud.org)
  • We characterize the activation kinetics of these reagents in vitro and demonstrate their efficacy in zebrafish embryos that express NfsB either ubiquitously or in defined cell populations. (cdc.gov)
  • Dissociated islet cells that are cultured in cell numbers by in vitro proliferation provide a promising platform for redifferentiation towards β-cells phenotype. (vt.edu)
  • We are working under the postulate that miRNAs are logical targets for in vitro experimentation because of their role in mediating pancreatic cell development. (ca.gov)
  • Aim 2 - Identify miRs targets through deep sequencing of RNA induced silencing complexes (RISC) in defined cell populations and assessment of their roles in differentiation in vitro and after experimental transplantation. (ca.gov)
  • Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control. (diabetesresearchconnection.org)
  • These cells display high aldehyde dehydrogenase activity (ALDH hi ), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDH lo cells. (prinsesmaximacentrum.nl)
  • Lastly, our results demonstrate that expression of differentiation markers can be uncoupled from the process of delamination of differentiating cells from the epithelium. (biomedcentral.com)
  • Moreover, during maturation in suspension culture, differentiating cells assembled in islet-like clusters, which expressed specific endocrine markers such as PDX1, SST, GCG and INS. (ox.ac.uk)
  • In early culture, PSCs are polygonal in shape with abundant lipid droplets in the cytoplasm ( Figure 1B ) and express stellate cell selective markers such as desmin, glial fibrillary acidic protein (GFAP), nestin, neural cell adhesion molecule, nerve growth factor, and synemin (34, 167). (pancreapedia.org)
  • CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. (biomedcentral.com)
  • Several significant scientific challenges still confront this potential therapy, including production of functional insulin-producing cells and understanding how the immune system would respond to hESC-derived therapeutic cell populations. (rotrf.org)
  • Transcriptome analysis of e14.5 progenitor single cells show distinct cell clustering populations in OGTKO Panc compared to littermate controls. (diabetesjournals.org)
  • 11 , 12 Light-dependent gene silencing can be achieved through whole-organism irradiation or the targeted illumination of specific cell populations. (cdc.gov)
  • We envisioned that enzyme-activatable cMOs could overcome these limitations, as the triggering enzymes could be expressed in individual cell populations using cis regulatory elements. (cdc.gov)
  • Gathering evidence suggests that some cell populations in early stage. (technuc.com)
  • Interestingly, gene expression profiling revealed that ALDH hi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. (prinsesmaximacentrum.nl)
  • Notably, when the glucagon signal was suppressed by genetic ablation or by chemicals, such as neutralising glucagon antibody, green-dominant cells emerged again in adult mice. (bvsalud.org)
  • Finally, we show that beta cell ablation in adult zebrafish triggers proliferation of ductal cells and their differentiation into Insulin- expressing cells. (refine.bio)
  • Conversation The 171099-57-3 ductal morphology of PDAC suggests that it derives from the ductal epithelium or from adult progenitor/stem cells capable of differentiating into duct-like cells. (technuc.com)
  • It was discovered that embryonic activation of KrasG12D in PDX1+ cells gives rise to common early neoplasms (1, 2, 38), whereas adult PDX1+ cells are considerably more resistant to KrasG12D-induced malignant change (39). (technuc.com)
  • More recent studies exhibited that adult acinar, islet, and centroacinar cells (intercalated duct cells located in the acinus) also have the potential to initiate invasive carcinoma, but each cellular context may require a different combination of genetic and/or environmental factors (3, 40, 41). (technuc.com)
  • Several transcription factors are expressed and repressed in a spatio-temporal manner in order to form and maintain adult pancreatic cell types. (biomedcentral.com)
  • The stomach and intestine are unique among endodermal organs in that they harbor large numbers of adult stem/progenitor cells that constantly produce epithelial cells, including hormone-secreting enteroendocrine cells (Barker et al. (diabetesresearchconnection.org)
  • We isolated CSCs from low passage PDAC cell lines derived from human tumors and commercially available cell lines. (amegroups.org)
  • Expression of EBF2 in the PDX1 and E-cadherin-expressing and organoid forming pancreatic epithelial CSCs indeed induced ductal and acinar-like structural differentiation in vivo in tumors resulting in tumor suppression. (amegroups.org)
  • Surprisingly, convincing evidence that pancreatic tumors can arise from ductal cells is usually scarce (36, 37). (technuc.com)
  • Pancreatic neuroendocrine neoplasms (PanNENs) fall into two subclasses: the well-differentiated, low- to high-grade pancreatic neuroendocrine tumors (PanNETs), and the poorly-differentiated, high-grade pancreatic neuroendocrine carcinomas (PanNECs). (biomedcentral.com)
  • With this approach, PanNENs fall into two basic subtypes: well-differentiated pancreatic neuroendocrine tumors (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs) [ 4 ]. (biomedcentral.com)
  • Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) hold great promise in the treatment of DM. (biomedcentral.com)
  • Mesenchymal stem cells (MSCs) have gained interest because of its potential application in regeneration medicine and cytotherapy. (biomedcentral.com)
  • Cancer stem cells (CSCs) and poorly differentiated progenitor cells in pancreatic ductal adenocarcinoma (PDAC) exacerbate hierarchical tissue organization contributing to cell hyperproliferation and therapy resistance. (amegroups.org)
  • Objectives Mesenchymal stem cells (MSCs) play an important role in the development and growth of tumor cells. (immune-source.com)
  • Of the several genetic factors that contribute to stem cells differentiation, miRNAs (microRNAs) are emerging as important determinants. (ca.gov)
  • Using exogenous stem cells to replace lost inner ear neurons is a potential strategy if stem cell-derived neurons can form central and peripheral connections, form synapses on hair cells and cochlear nucleus neurons, and re-establish functional and tonotopic circuits [ 6 ]. (biomedcentral.com)
  • We address these potential limitations by adopting the technique of blastocyst complementation (BC) to generate inner ear neurons from induced pluripotent stem cells (iPSCs). (biomedcentral.com)
  • 3) We are defining the properties of cancer stem cells that initiate and sustain the unique disease features of acute leukemias through the use of various adoptive animal models. (stanford.edu)
  • The present invention provides methods to promote the differentiation of pluripotent stem cells. (patsnap.com)
  • The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer. (patsnap.com)
  • Our objective is to examine whether/how Gαo regulates islet development and insulin secretion in β-cells. (diabetesjournals.org)
  • however, it remains unclear precisely when, and from where, alpha cells emerge and what regulates alpha cell fate. (bvsalud.org)
  • Ectopic expression of DOCK8 regulates lysosome-mediated pancreatic tumor cell invasion. (mayo.edu)
  • Genetic studies have shown that formation of pancreatic endocrine cells in mice is dependent on the cell autonomous action of the bHLH transcription factor Neurogenin3 and that the extent and timing of endocrine differentiation is controlled by Notch signaling. (biomedcentral.com)
  • or = 0.02 ng/ml of mGLP-1 facilitated cell proliferation and 0.1 ng/ml and 0.5 ng/ml of mGLP-1 rescued SH-SY5Y cells from Abeta(1-42)-induced apoptosis. (ncbcs.org)
  • Mechanistically, EBF2 uniformly activates Pparγ-expression in pancreatic cancer cells and limits cell proliferation, whereas oncogenic drivers are expressed differentially in the progenitor cell subsets. (amegroups.org)
  • The complex PDAC pathobiology is established predominantly through KRAS mutations and the associated cellular signaling that contributes to cell proliferation and dedifferentiation ( 5 , 6 ). (amegroups.org)
  • Furthermore, Imeg + Met treatment increased ß-cell mass by enhancing ß-cell proliferation and ameliorating ß-cell apoptosis in db/db mice. (bvsalud.org)
  • The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and/or stimulate cells that maximizes stimulation and/or proliferation of such cells. (patsnap.com)
  • In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and/or cell surface moiety aggregation. (patsnap.com)
  • Overall, these studies will test whether human PDX1+ cells stimulate an allogeneic adaptive immune response in vivo and provide a platform for restoration of lost b cell function. (rotrf.org)
  • The aim of this study was to optimize an efficient differentiation protocol that mimics in vivo pancreatic organogenesis and to investigate whether RSV may improve the final maturation step to obtain functional insulin-secreting cells. (ox.ac.uk)
  • Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin+ cells with close molecular and functional similarity to β cells. (diabetesresearchconnection.org)
  • However, the islet cells can only be observed at 52 days post-fertilization. (wikipedia.org)
  • All islet cells can be observed in the first trimester in human. (wikipedia.org)
  • This variation in the development of islet cell subtypes is due to differential gene expression and induction pathways of progenitor cells. (wikipedia.org)
  • High glucose media enhanced insulin expression by about 4-18 fold, suggesting a glucose-dependent effect in the proliferated islet-derived cells. (vt.edu)
  • This led us to question whether excessive Ca V 3 channels, retained mistakenly in engineered human-induced pluripotent stem cell-derived islet (hiPSC-islet) cells, act as an obstacle to hiPSC-islet maturation. (mdpi.com)
  • Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. (prinsesmaximacentrum.nl)
  • We hypothesized that OGT, expressed at a very high level in β-cells, has key developmental regulatory properties. (diabetesjournals.org)
  • Increasingly, complimentary cell culture techniques, which recapitulate the developmental microenvironment, are employed to coax cells to adopt new identities by indirectly regulating transcription factor activity via intracellular signalling pathways. (silverchair.com)
  • To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology. (frontiersin.org)
  • Organogenesis is a complex developmental process requiring hierarchical cell and tissue differentiation, coordinated in time and space in response to changes in local and distant signaling cues. (biomedcentral.com)
  • Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)
  • The origination of the pancreatic tissue is from the dorsal and ventral aspects of the posterior foregut. (wikipedia.org)
  • Owing to the shortage of donor tissue, attempts are being made to develop alternative sources of insulin-secreting cells. (vt.edu)
  • The cells proliferated well in tissue culture plates and were subcultured for no more than 5 passages. (vt.edu)
  • The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin+ cells after undergoing cellular reprogramming. (diabetesresearchconnection.org)
  • To further understand the mechanism by which Notch exerts this function, we have investigated pancreatic endocrine development in chicken embryos. (biomedcentral.com)
  • Transcriptome analysis of Gcg-Timer embryos revealed that the mRNAs related to angiogenesis were enriched in newly generated alpha cells. (bvsalud.org)
  • In this study, we characterize, in zebrafish embryos, the pancreatic lateral plate mesoderm, which is located adjacent to the ventral pancreatic bud and is essential for its specification and growth. (biologists.com)
  • In tail bud embryos, vpp1 expression specifically demarcates two ventral pancreatic buds, whereas hhex expression is mainly restricted to the liver diverticulum . (xenbase.org)
  • Although studies have identified unique transcription factors in the selection of normal pancreatic lineages, the cells of origin and molecular mechanisms arbitrating PDAC growth are poorly defined. (amegroups.org)
  • In health, the process of fibrogenesis is a well-regulated dynamic process which is necessary for regular turnover of extracellular matrix (ECM) that allows remodeling and maintenance of normal pancreatic architecture. (pancreapedia.org)
  • Few mice that grow into adulthood develop overt diabetes due to functional β-cell mass failure. (diabetesjournals.org)
  • cancer cells can develop from both types of functional cells. (medicinenet.com)
  • Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. (diabetesresearchconnection.org)
  • Major progress has been made in recent years to produce functional insulin+ cells for cell replacement therapies to treat diabetes. (diabetesresearchconnection.org)
  • We sought to devise improved strategies to derive functional insulin-secreting (insulin+) cells from GI tissues and to harness the regenerative capacity of these tissues as a renewable source of β cells. (diabetesresearchconnection.org)
  • BC is the only current method for making fully functional, three-dimensional organs from pluripotent cells and generating human organs in large mammalian hosts may be able to address the critical worldwide problem of organ shortages for transplantation [ 16 ]. (biomedcentral.com)
  • One gene Onecut1/Hnf6 (onecut domain family member 1 transcription factor) is also responsible for the timely expression of Pdx1 in both the ventral and dorsal buds. (wikipedia.org)
  • Furthermore, titration of hhex with a dexamethasone-inducible hhex -VP16GR fusion construct suggested that endogenous hhex activity during gastrulation is essential for the formation of ventral pancreatic progenitor cells. (xenbase.org)
  • miR-122 is not expressed in DE, but increases in levels to coincide with lower miR-375 expression as a more heterogeneous mixture of cells form as DE differentiates into multiple lineages. (ca.gov)
  • The first mouse models of PDAC were generated by combining KrasG12D activation in embryonic pancreatic progenitors (using the PDX1 promoter) with homozygous deletion of p53 or CDKN2A (1, 2, 26). (technuc.com)
  • Here we show that the brown adipose differentiation gene, EBF2, activates differentiation-associated signals in the cancer progenitor cells in culture and CSC transplantation models. (amegroups.org)
  • In combination with transgenic organisms, such enzyme-actuated antisense tools will enable gene silencing in specific cell types, including tissues that are not amenable to optical targeting. (cdc.gov)
  • We are studying the role that normal chromatin structure plays in gene regulation in hematopoietic cells and how its disruption leads to altered development and cancer. (stanford.edu)
  • The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors produced by CD8+ T-cells. (cancerindex.org)
  • We therefore explored the spatial and transcriptional heterogeneity of alpha cell differentiation using a novel time-resolved reporter system. (bvsalud.org)
  • Cellular identity is determined by the transcriptional profile which comprises the subset of mRNAs, and therefore proteins, being expressed by a cell at a given point in time. (silverchair.com)
  • show that the antral stomach region of the gastrointestinal tract is particularly amenable to being reprogrammed to a β cell fate because of transcriptional similarity and that bioengineered stomach mini-organs containing reprogrammed cells can rescue hyperglycemia when transplanted into diabetic mice. (diabetesresearchconnection.org)
  • We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. (stanford.edu)
  • For example, in normal mouse development, pancreatic progenitor cells express the proteins Sox17 and Pdx1 around embryonic day 8.5. (livingwithdiabetes.info)
  • This study reveals a previously unrecognized function of EBF2 in regulating PDAC progenitor cell differentiation and tumor suppression. (amegroups.org)
  • More importantly, these PDX1+ cells are fully qualified to form PanINs on activation of Kras alone and, in conjunction with p53 mutation or INK4A deletion, can develop into invasive and metastatic PDAC (2, 4, 38). (technuc.com)
  • PanNECs can occur with admixed components of other carcinoma types of non-neuroendocrine origin, this can be either ductal adenocarcinoma (PDAC) or acinar cell carcinoma (ACC). (biomedcentral.com)
  • Chemotherapy for metastatic pancreatic cancer can extend the life and improve the quality of life, but it rarely cures the patient. (medicinenet.com)
  • Pancreatic cancer is usually characterized by aggressive growth and a high propensity for metastatic spread. (technuc.com)
  • We show that endogenous manifestation of oncogenic KrasG12D induces growth of PDX1+ 171099-57-3 cells and endows them with high propensity for metastatic dissemination while still at premalignant stages. (technuc.com)
  • The purchase of metastatic properties by tumor cells is usually often considered a late event in neoplastic progression, although it has long been argued that certain genetic changes that are selected for the proliferative advantage they confer to main tumor cells may also confer invasive and metastatic phenotypes (45, 46). (technuc.com)
  • Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. (biomedcentral.com)
  • These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention. (biomedcentral.com)
  • CTCs analysis through liquid biopsies provides not only a full repertoire of tumor biological material (including proteins, lipids, sugars and nucleic acids) but also a sample of living tumor cells endowed with metastatic ability [ 3 ]. (biomedcentral.com)
  • In amniotes, the pancreatic mesenchyme plays a crucial role in pancreatic epithelium growth, notably through the secretion of fibroblast growth factors. (biologists.com)
  • Deletion of the only nutrient-sensor enzyme, O-GlcNAc Transferase (OGT), catalyzing O-GlcNAc addition onto target proteins in pancreatic β-cells induces diabetes through β-cell failure. (diabetesjournals.org)
  • Recombinant Human Wnt-3a (Catalog # 5036-WN) induces alkaline phosphatase production by the MC3T3-E1 mouse preosteoblast cell line. (novusbio.com)
  • The endocrine cells constitute the beta cells which make insulin, alpha cells which secrete glucagon, delta cells which secrete somatostatin and the PP-cells which secrete pancreatic polypeptide. (wikipedia.org)
  • We studied tumor cell signaling in the cell subsets to understand the tumor-inhibitory potentials of EBF2. (amegroups.org)
  • In this study, we generate transgenic mice expressing pHluorin-LC3-mCherry reporter for monitoring systemic autophagic flux by measuring the pHluorin/mCherry ratio, validating them in the starvation and insulin-deficient model. (bvsalud.org)
  • A better understanding of the levers governing transcription factor activity benefits our ability to generate therapeutic cell types at will. (silverchair.com)
  • Here, we explore the evolution of reprogramming and directed differentiation approaches within the context of hepatocyte to β-cell transdifferentiation focussing on how the introduction of new techniques has improved our ability to generate β-cells. (silverchair.com)
  • Aim 1 - Generate miR expression profiles using deep sequencing for defined stages of development from pluripotent to endocrine cells and select candidate miRs for manipulations involving silencing and overexpression. (ca.gov)
  • Ongoing research in our laboratory is directed at deriving β-cells from hESCs. (ca.gov)
  • Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y cells from apoptosis induced by amyloid-beta peptide (1-42). (ncbcs.org)
  • Activation of the glucagon-like peptide-1 receptor (GLP-1R) upon ligand binding results in the discharge of insulin from pancreatic cells. (ncbcs.org)
  • Despite extensive research, targeted therapies for pancreatic ductal adenocarcinoma (PDCA) patients thus far benefited only marginally due to recurring mutations and intratumor heterogeneity ( 1 , 4 ). (amegroups.org)
  • But this genetic blueprint only gets turned on at certain times and in certain cells, when the proper signals are present. (livingwithdiabetes.info)
  • We consider how, over the last 20 years, advances in genetic engineering and cell culture techniques have improved the efficiency and efficacy of the transdifferentiation process and brought us closer to a clinically relevant therapy for type 1 diabetes (T1D). (silverchair.com)
  • In addition to these basic issues concerning leukemia pathogenesis, we are devising new diagnostic procedures for detecting and monitoring leukemia patients based on molecular genetic abnormalities in the malignant cells. (stanford.edu)
  • Methods: Primary mouse enteric neurons (EN) were exposed to a conditioned medium from ACE2-expressing Caco-2 colonic epithelial cells infected with SARS-CoV-2 or treated with tunicamycin (ER stress inducer). (emory.edu)
  • Pancreatic progenitor cells have been shown to arise from cells originating from the developing foregut during mammalian development. (wikipedia.org)
  • We conclude that pancreatic endocrine development in the chicken relies on a conserved bHLH cascade under inhibitory control of Notch signaling. (biomedcentral.com)
  • The development of isolation and culture methods for PSCs in 1998 helped to unravel the mechanisms involved in the process of pancreatic fibrogenesis (5, 11) and also helped researchers to investigate the functions of these cells both in health and disease. (pancreapedia.org)
  • This current work goals to look at whether or not mGLP-1 attenuates Abeta(1-42)-mediated cytotoxicity in SH-SY5Y cells and to discover the attainable mechanisms. (ncbcs.org)
  • Imeglimin and metformin act in metabolic organs, including ß-cells, via different mechanisms. (bvsalud.org)
  • However, though BC is emerging as a potential organ transplant option, challenges regarding organ size scalability, immune system incompatibilities, long-term maintenance, potential evolutionary distance, or unveiled mechanisms between donor and host cells remain. (frontiersin.org)
  • In this study we investigated the mechanisms involved in the induction of oxidative stress and impairment of mitochondrial quality control and mitophagy in hepatocytes by the saturated fatty acid palmitate and Western diet feeding in mice and if their harmful effects could be reversed by the neurotrophic factor glial cell derived neurotrophic factor (GDNF). (emory.edu)
  • These vectors efficiently express multiple transcription factors and stimulate insulin promoter activity in a combinatorial manner. (elsevierpure.com)
  • The present invention relates generally to methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells that maximizes the expansion of such cells to achieve dramatically high densities. (patsnap.com)
  • In the present study, we investigated the impacts of imeglimin, metformin, or their combination (Imeg + Met) on ß-cells, the liver, and adipose tissues in db/db mice. (bvsalud.org)
  • We have generated a reporter cell lines that can distinguish pancreatic cells from liver cells in post-DE differentiation, and possibly mature beta cells from other endocrine cells. (ca.gov)
  • Here, we discuss how transcription factors, and their unique position as the gatekeepers of cellular identity, are exploited in cell reprogramming protocols by exploring work focusing on one reprogramming paradigm - the transdifferentiation of hepatocytes to pancreatic beta cells (β-cell). (silverchair.com)
  • citation needed] Pdx1 is accepted as the earliest marker for pancreatic differentiation. (wikipedia.org)
  • Pdx1 has been shown to be a marker for all pancreatic and mid-gut progenitor cells. (wikipedia.org)
  • Photomicrograph showing a normal rat pancreatic section immunostained for the stellate cell selective marker desmin (left) and a corresponding line diagram (right). (pancreapedia.org)
  • Results: SARS-CoV-2 infection led to increased expression of BiP/GRP78, a marker and key regulator for ER stress in Caco-2 cells. (emory.edu)