Emerging evidence suggests that microRNA (miRNA)-mediated post-transcriptional gene regulation plays an essential role in modulating embryonic stem (ES) cell pluripotency maintenance, differentiation, and reprogramming of somatic cells to an ES cell-like state. Investigations from ES cell-enriched miRNAs, such as mouse miR-290 cluster and human miR-302 cluster, and ES cell-depleted miRNAs such as let-7 family miRNAs, revealed a common theme that miRNAs target diverse cellular processes including cell cycle regulators, signaling pathway effectors, transcription factors, and epigenetic modifiers and shape their protein output. The combinatorial effects downstream of miRNA action allow miRNAs to modulate cell-fate decisions effectively. Furthermore, the transcription and biogenesis of miRNAs are also tightly regulated. Thus, elucidating the interplay between miRNAs and other modes of gene regulation will shed new light on the biology of pluripotent stem cells and somatic cell reprogramming. ...
Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in
In a recent issue of Cell Stem Cell, Morrisey and colleagues [3] report that iPSCs can be generated solely through the expression of a set of miRNAs, thereby avoiding all original Yamanaka factors for the first time. This breakthrough is destined to expand our understanding of the pathways that drive reprogramming. Using lentivirus-based expression of the miR-302/367 cluster to reprogram both mouse and human cells, Morrisey and colleagues [3] show that miRNA-based reprogramming proceeds faster than with standard four-factor reprogramming. Consistent with this finding, pluripotency genes such as Sox2, Nanog and Rex1 are upregulated earlier in fibroblasts expressing the miR-302/367 cluster than in fibroblasts transduced with the four transcription factors. Using a mouse line expressing a reporter gene with the Oct4 promoter driving green fluorescent protein, the authors [3] also show that the endogenous Oct4 locus is reactivated to a greater extent following miRNA expression than without miRNA ...
The dramatic discovery that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs), by the expression of just four factors, has opened new opportunities for regenerative medicine and novel ways of modeling human diseases. Extensive research over the short time since the first iPSCs were generated has yielded the ability to reprogram various cell types using a diverse range of methods. However the duration, efficiency, and safety of induced reprogramming have remained a persistent limitation to achieving a robust experimental and therapeutic system. The field has worked to resolve these issues through technological advances using non-integrative approaches, factor replacement or complementation with microRNA, shRNA and drugs. Despite these advances, the molecular mechanisms underlying the reprogramming process remain poorly understood. Recently, through the use of inducible secondary reprogramming systems, researchers have now accessed more rigorous mechanistic experiments to
Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique ...
Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. Here, we show that mouse fibroblasts can be directly converted into neuronal cells using only a cocktail of small molecules, with a yield of up to |90% being TUJ1-positive after 16 days of induction. After a further maturation stage, these chemically induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET151, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle for chemically induced direct reprogramming of somatic cell fates across
Researchers are still fascinated by the idea of the possibility of reprogramming the cells of any tissue, turning them into cells with the capacity to differentiate into cells of a completely different type - pluripotent cells - and they are still striving to understand how it happens. A group from Spain publishes this week an article on the discovery of a new gene called TRF1 that is essential for nuclear reprogramming.
Results. All studied iPSC-lines except one Geltrex®-line lost at p. 9 showed successful reprogramming with no qualitative differences between sendai-virally or episomally reprogrammed lines. The lines that were cultured feeder-free stained positive for neural markers, and differentiated, neural precursor-like cells were present at all passages, which was not encountered for MEF-cultured lines. For the two cardiac-differentiated lines, the efficiency of differentiation assessed in two ways showed a more efficient differentiation of the sendai-virally reprogrammed line than the one reprogrammed with episomal plasmids. Gene expression studies showed no significant changes in pluripotency gene expression between lines or passages except for the gene NANOG, the expression of which was lower in the later passage than the earlier passage. The reprogramming efficiencies observed were extremely low, in the range of 0,005-0,017 ...
Objective: Induced pluripotent stem (iPS) cells are bioengineered from somatic sources to acquire embryonic-like developmental potential. This study aims to evaluate the impact of imposed stemness load on the cardiogenic competency required for bona fide regenerative applications of iPS cells.. Rationale: Nuclear reprogramming inculcates pluripotent capacity by which de novo tissue differentiation is enabled. Yet, introduction of ectopic reprogramming factors imposes a stemness burden that may desynchronize natural developmental schedules and confound cardiac lineage specification.. Methods: Targeted inclusion and exclusion of reprogramming transgenes (c-MYC, KLF4, OCT4 and SOX2) was achieved using a drug-inducible and removable cassette according to the piggyBac transposon/transposase system.. Results: Pulsed transgene overexpression, prior to iPS cell differentiation, hindered cardiogenic outcomes. Transgene removal enabled proficient differentiation of iPS cells into cardiac tissue, not ...
Since the pioneer work published by Takahashi & Yamanaka, the technique of reprogramming cells from a differentiated to an embryonic-like status has experienced an exploding development in regard to both techniques and applications. The most obvious application is the use in tissue regeneration. However, two key obstacles need to be overcome for clinical realization, i.e. risk of reprogrammed cells to develop neoplasiae as well as cumbersome and costly cell culture procedures. Therefore, it is imperative to develop cost-efficient methods with a lower the risk of cancer. The present invention has solved this problem by using a modification of the originally described method. Here, the transcription factors Sox2, cMyc and Klf4 are exogenously and stably expressed, whereas Oct4 is introduced with an exogenous transient expression system. This method is qualified to produce autologous neural stem cells that proliferate indefinitely and are able to re-differentiate into functional neural cells. The ...
Nuclear reprogramming demonstrates the potential for reversability in cellular differentiation. Reprogramming introduces a small number of transcription factors into somatic cells, such as skin cells, transforming the skin cells into induced pluripotent stem cells (iPS), While a core set of factors necessary for reprogramming has been identified the process is extremely inefficient (less than .1% of cells exposed to factors are transformed). The impetus to improve the efficiency of reprogramming is high. Approaches in regenerative medicine, such as replacing organs and tissues lost to injury and disease, face the obstacle of donor cell rejection by the host. Nuclear reprogramming can create iPS cells that are genetically identical to that of the donor, thus allowing a patient to be the donor for an iPS cell line that may serve as starting material for replacement tissue and organs which will not be rejected by the patient. A key component to increasing the efficiency of reprogramming is a more ...
The LIF-regulated Jak/Stat3 pathway is important for naïve-state pluripotency establishment across species (Weinberger et al., 2016). Although many downstream targets of Stat3 have been reported, the complete understanding of Jak/Stat3 mediated pluripotency establishment has not been achieved. Jak/Stat3 signaling has been reported to regulate pluripotency in pluripotent stem cells through a number of transcription factors such as Tfcp2l1 and Klf4 (Hall et al., 2009; Martello et al., 2013; Niwa et al., 2009; Ye et al., 2013). However, how Jak/Stat3 regulates downstream targets in reprogrammed somatic cells to achieve complete pluripotency is not well understood. We found that in mouse iPSC generation, LIF-stimulated Jak activity regulates the activation of a number of key pluripotent factors such as Esrrb. To the best of our knowledge, this is the first report demonstrating Esrrb as a downstream target of LIF/Jak signaling in somatic cell reprogramming. Esrrb is a naïve-specific pluripotency ...
If you have a question about this talk, please contact Dr Xavier Moya.. Nuclear transplantation to eggs and oocytes can reprogram somatic cell nuclei from an adult pattern of gene expression to that characteristic of embryos. This is the first stage of a procedure by which replacement cells can be formed from adult cells of the same individual, thereby eliminating the need for immunosuppression. A central aim of recent work in this field is to analyze the mechanisms by which eggs and ooctyes can rejuvenate a cell from an adult to an embryonic state.. This talk is part of the Wolfson College Science Society talks series.. ...
Heterogeneous gene expressions of cells are widely observed in self-renewing pluripotent stem cells, suggesting possible coexistence of multiple cellular states with distinct characteristics. Though the elements regulating cellular states have been identified, the underlying dynamic mechanisms and the significance of such cellular heterogeneity remain elusive. We present a gene regulatory network model to investigate the bimodal Nanog distribution in stem cells. Our model reveals a novel role of dynamic conversion between the cellular states of high and low Nanog levels. Model simulations demonstrate that the low-Nanog state benefits cell differentiation through serving as an intermediate state to reduce the barrier of transition. Interestingly, the existence of low-Nanog state dynamically slows down the reprogramming process, and additional Nanog activation is found to be essential to quickly attaining the fully reprogrammed cell state. Nanog has been recognized as a critical pluripotency gene in stem
Induced pluripotent stem cells (iPSCs), generated from somatic cells by overexpression of transcription factors, Oct4, Sox2, Klf4, and c-Myc, have the same characteristics as pluripotent embryonic stem cells (ESCs). iPSCs reprogrammed from differentiated cells undergo epigenetic modification during reprogramming, and ultimately acquire a similar epigenetic state to that of ESCs. In this study, these epigenetic changes were observed in reprogramming of uniparental parthenogenetic somatic cells. The parthenogenetic pattern of imprinted genes changes during the generation of parthenogenetic maternal iPSCs (miPSCs), a process referred to as pluripotent reprogramming. Here, we determined whether altered imprinted genes are maintained or reverted to the parthenogenetic state when the reprogrammed cells are redifferentiated into specialized cell types. To address this question, we redifferentiated miPSCs into neural stem cells (miPS-NSCs) and compared them with biparental female NSCs (fNSCs) and ...
Direct Reprogramming Science Project: Investigate how transcription factors can be used to turn one cell type directly into another cell type, and why this technique is important for the future of the field of regenerative medicine.
Recent research on iPS cells supports the hypothesis that cancer stem cells may arise through a "reprogramming-like" mechanism (38). By enforcing the expression of a set of genes, the so-called reprogramming factors, differentiated somatic cells can be converted to iPS cells, which have the same capabilities as ES cells to give rise to all tissue types of the body. Interestingly, most of these reprogramming factors are overexpressed or upregulated in certain types of human tumors, and at least some of them (e.g., c-MYC, KLF4, SOX2, and LIN28) are established or putative oncogenes (38). Moreover, five independent studies have shown that disabling p53, an essential tumor-suppressor gene, remarkably improves the efficiency of iPS cell production (38). Therefore, there may be overlapping mechanisms that control the functions and maintenance of iPS cells and cancer stem cells (38). LIN28, one of reprogramming factors discussed above, is very restricted in its expression; it is found only in ES cells, ...
While studying a rare genetic disease, researchers discovered a signaling pathway linked to the efficiency of reprogramming somatic cells into stem cells.
Our lab tries to understand the molecular mechanisms underlying pluripotency and nuclear reprogramming. Pluripotency denotes the ability of cells, such as embryonic stem (ES) cells, to give rise to all cell types of the mammalian body, while nuclear reprogramming is the dedifferentiation of a specialized cell back into a pluripotent state. Reprogramming does not normally occur in vivo but can be achieved experimentally by nuclear transfer, ES cell-somatic cell fusion and by directly inducing embryonic genes in somatic cells, generating so-called induced pluripotent (iPS) stem cells ...
The success of inducing pluripotency in primary fibroblasts and other cells with a combination of only a small number of transcription factors suggested that fully differentiated cells might change fate following similar treatments. Since the demonstration of induced pluripotent stem cells (iPSCs), at least three examples have been published where 3 cell type-specific factors were selected from a pool of 10-20 candidates that, when expressed from viral vectors, could induce beta-cells, neurons, or cardiomyocytes.. Induced beta-cells [1]: Ngn3, Pdx1, and Mafa, adenovirus injected to in vivo targets. Induced neurons (iN) [2]: Ascl1, Brn2, and Myt1l, lentivirus infecting mouse embryonic fibroblasts (MEF) or tail tip fibroblasts (TTF). Induced cardiomyocytes (iCM) [3]: Gata4, Mef2c, and Tbx5, lentivirus infecting cardiac fibroblasts or TTF. In all 3 cases, the change of fate seemed to be via direct conversion, without passing through a progenitor cell fate before further differentiation. Like iPSC ...
Induced Pluripotent Stem Cells (IPSCs) are stem cells that can be derived from fibroblast cells (skin). It has the potential of providing multiple tissue types in the body without any transplant rejection and also bypasses the ethical issues of embryonic stem cells. However, because parts of the cellular mechanisms for reprogramming are still unclear, IPSCs has yet to be utilized in the clinical setting since scientists cannot control the reprogramming/ differentiation process precisely. Here we present a microfluidic chip, which can be used for deciphering reprogramming dynamics. This chip can pair and fuse different cell types in the single cell level for IPSCs reprogramming studies. It has been shown the most efficient stem cell reprogramming method is via cell fusion (70%). We demonstrate the ability of single cell pairing of stem cells to fibroblasts with high efficiency. We then show the feasibility of electro-fusing these cells on chip. Furthermore, we explore the possibility of utilizing ...
Induced Pluripotent Stem Cells (IPSCs) are stem cells that can be derived from fibroblast cells (skin). It has the potential of providing multiple tissue types in the body without any transplant rejection and also bypasses the ethical issues of embryonic stem cells. However, because parts of the cellular mechanisms for reprogramming are still unclear, IPSCs has yet to be utilized in the clinical setting since scientists cannot control the reprogramming/ differentiation process precisely. Here we present a microfluidic chip, which can be used for deciphering reprogramming dynamics. This chip can pair and fuse different cell types in the single cell level for IPSCs reprogramming studies. It has been shown the most efficient stem cell reprogramming method is via cell fusion (70%). We demonstrate the ability of single cell pairing of stem cells to fibroblasts with high efficiency. We then show the feasibility of electro-fusing these cells on chip. Furthermore, we explore the possibility of utilizing ...
Q&A about the Direct Reprogramming Breakthrough. Answering Common Claims about "direct reprogramming" that creates induced pluripotent stem cells (iPSCs), an ethically unproblematic alternative to human embryonic stem cells (hESCs).. Claim 1: Good science demands that we investigate all avenues of inquiry, including cloning human embryos. Response: "Good" research respects both scientific and ethical standards. iPSC research meets every mark of good science and has the following ethical advantages: it does not destroy human embryos; it does not use human oocytes; and it does not alienate a large part of the countrys citizens by engaging in research that they find deeply immoral. Claim 2: Politicians should continue to pursue federal funding for the use of so-called "left over" IVF embryos despite the recent advance of iPSCs.. Response: Direct reprogramming to create iPSCs provides a scientifically feasible and promising alternative to research that requires destroying human embryos. Even ...
The Simplicon™ RNA Reprogramming Technology is a next generation reprogramming system that uses a single synthetic, polycistronic self-replicating RNA strand engineered to mimic cellular RNA to generate human iPS cells.
Harvard Stem Cell Institute (HSCI) researchers, have demonstrated that adult cells, reprogrammed into another cell type in a living animal, can remain functional over a long period.
Cells from the rare individuals who naturally control HIV infection have been the focus of investigation for nearly 15 years with the aim of elucidating their specific features.
The generation of induced pluripotent stem cells (iPSCs) has revolutionised the stem cell field, opening up avenues for both basic and translational research. However, there is still much to understand about the mechanisms underlying reprogramming to the iPSC state, particularly in human. On p. 15, Takashi Tada and colleagues report the isolation of stable intermediately reprogrammed stem cells (iRSCs) that are paused in their progression to pluripotency. These cells, generated by transient expression of the reprogramming factors Oct4, Klf4, Sox2 and c-Myc, express some pluripotency markers, such as endogenous SOX2 and NANOG, but have not yet undergone mesenchymal-to-epithelial transition (MET) or upregulated endogenous OCT4. The iRSC lines are stable over multiple generations, but can easily and efficiently be induced to continue reprogramming to an iPSC-like state by culture at high density. The authors use these iRSC lines to characterise the order of events during reprogramming, finding ...
ReproTeSR™, a specialized medium for iPS cell generation supports efficient reprogramming of erythroid or CD34+ cells expanded from peripheral blood.
How do cells differentiate and switch between alternate phenotypic states? Classic views of cell development were built on the idea that pluripotent progenitor cells progress in a unidirectional manner to the differentiated state. But given the numerous observations of transdifferentiation and cellular reprogramming events, we now appreciate that perhaps all cell types-even those that are terminally differentiated-have the capacity to access other phenotypic states. During these switches in cell phenotype, it is clear that the master regulatory transcription factors that specify a new cell lineage must be activated, but we know surprisingly little about the other half of these transitions: the fate of the master regulators that had promoted and defined the previous cell state. The ubiquitin-proteasome system (UPS) has been implicated by the few studied examples of normal differentiation pathways, but the crucial question remains: how does the UPS erase the previous phenotypic state and promote ...
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Next, we tested these new factors in selection‐free reprogramming of MEFs on the basis of a three‐factor (OCT4, SOX2 and KLF4; referred to as OSK) or a four‐factor system (OSK plus NANOG; OSKN). When the native OSKs were introduced into MEFs carrying the Oct4‐GFP transgene as a reprogramming reporter, we obtained 3±1 (mean±s.d.; n=3) green fluorescent protein (GFP)‐positive colonies from 5 × 104 transduced fibroblasts at day 16 (Fig 1C). By contrast, when OCT4-VP16 was used to replace OCT4 in the co‐transduction with SOX2 and KLF4 (XSK), we obtained 236±35 GFP+ colonies; a 78‐fold increase. Similarly, replacement of SOX2 with SOX2-VP16 (OYK) resulted in 108±19 GFP+ colonies, a 36‐fold increase. When NANOG-VP16 was used to replace NANOG (N) in the four‐factor system (OSKZ), we obtained 95±27 colonies, 19 times the number obtained from the transduction with the native factors (5±3; OSKN). The combination of all three synthetic factors in the four‐factor system generated ...
Biological and biomedical experiments are increasingly producing large datasets of excellent quality, spanning diverse phenomena such as evolution, cell differentiation, disease mechanisms, and many others. We are interested in applying Statistical Mechanics methods to understand some of those phenomena.. One problem we are particularly interested in is cell reprogramming. Recent experiments have shown that, by forcing the overexpression of a few genes, the usual direction of cell differentiation can be reversed. Differentiated cells can be "reprogrammed" to become induced pluripotent stem (iPS) cells, which are capable of reproducing and developing into any cell type in the body. This discovery has completely changed the standard view about cell specialisation, and it has wide potential implications, particularly in medicine. The reprogramming technology has been used to obtain blood samples from patients, generate iPS cells, and from them generate diseased heart or brain tissues with the exact ...
Overexpression of four factors (Oct4, Sox2, Klf4, Myc, or Oct4, Sox2, Nanog, Lin28) reprogram somatic cells to become induced pluripotent stem (iPS) cells. Reprogramming accompanies genetic and epigenetic changes, and its molecular mechanism is still unknown. We recently showed that in iPS cells the global DNA methylation status is close to that of human embryonic stem (hES) cells, suggesting the epigenetic resetting during reprogramming. Furthermore, we have showed the possible dissection of stages in reprogramming through live cell imaging analysis ...
Last year, George Daleys team found that iPSCs carry a memory of their past identities even after theyve been reprogrammed. They have molecular marks that annotate their DNA and affect which genes are active. These "epigenetic" marks are like Post-It notes stuck in a book - they tell you which parts to read and which to ignore. They also constrain the future of the iPSCs - for example, they make it easier to produce blood cells from iPSCs that came from blood cells as opposed to, say, skin cells. And last month, Joseph Eckers group found even more epigenetic differences between iPSCs and ESCs than anyone had suspected.. Now, two other teams have found that reprogramming cells also changes their very DNA, so that the genomes of iPSCs are slightly different to those of the adult cells they came from. This isnt just a case of different Post-It notes - the underlying text has also changed. And some of these mutations affect genes that are involved in cancer or genetic disorders.. These concerns ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Theres some big, positive news on the stem cell front today. Two new innovative papers both by teams led by Sheng Ding of Gladstone Institutes with UCSF report all-chemical direct reprogramming of human somatic cells. Dings team took skin cells and by exposing them to cocktails of small molecules was able to turn them directly into precursors for heart muscle and neural cells. The two direct reprogramming papers were published in Science here and in Cell Stem Cell here. The former paper is Cao, et al. and the latter is Zhang, …Read More. ...
A large international collaboration headed by researchers at the University of Copenhagen has identified an essential mechanism that controls wound healing in the intestine. The new discovery shows that the cells in the intestines are reprogrammed and take on a foetal-like state, which is vital to intestinal cells ability to heal wounds in the intestine. 
Screening an RNAi library against chromatin regulating genes we previously identified that the highly conserved protein LIN-53/Rbbp4/7, which is a component of several chromatin-regulating complexes such as the chromatin-silencing PRC2, protects germ cells from being reprogrammed into specific somatic fates. Germ cells of animals that have been treated with lin-53 RNAi can be converted directly into ASE-like glutamatergic neurons upon ectopic expression of CHE-1. Additionally, ongoing screens revealed mutants or RNAi-depleted animals in which different somatic tissues such as the hypodermis (skin) our intestine (gut) respond to induced reprogramming. Our goal is to systematically apply high-throughput genetic as well as molecular and biochemical methods to understand how direct cell fate reprogramming is inhibited and the regulatory networks that are involved. The BIMSB provides a tremendous amount of technology and omic platforms. While our lab owns the BioSorter® (Union Biomterica) for ...
Some diverse new stem cell papers worth a peek this weekend? Direct reprogramming hits crest: Generation of Multipotent Induced Neural Crest by Direct Reprogramming of Human Postnatal Fibroblasts with a Single Transcription Factor, Cell Stem Cell Hormone receptors in prostate cancer cells […]. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA Warren L, et al. Cell Stem Cell (2010) 7:618- ...
In our lab, we leverage natural killer cells, alongside other cells of the immune system, as powerful tools for the treatment of malignant diseases. Their ability to calibrate a sophisticated repertoire of activating and inhibitory receptors places them in the unique realm of both adaptive and innate immunity which includes memory and education. Regulation of these cells responses to these receptors, while understanding metabolic reprogramming mechanisms, is a focus of our labs work ...
Scientists have successfully changed the identity of one type of cell into another in living mice, potentially paving the way for new developments in the growth of replacement tissues used to treat a broad spectrum of diseases.. Researchers were able to transform ordinary pancreas cells into a rare type that creates insulin, which may provide future help for those who suffer from diabetes. Whats more, scientists say this development could reach much further than possible treatments for diabetes. It could lead to treatments like growing new heart cells after a heart attack or nerve cells to treat disorders like ALS, also known as Lou Gehrigs disease. The work is "a major leap" in reprogramming cells from one kind to another, said one expert not involved in the research, John Gearhart of the University of Pennsylvania.. Thats because the feat was performed in living mice rather than a lab dish, the process was efficient and it was achieved directly without going through a middleman like ...
In all known cases of transcription factor (TF)-based reprogramming, the process is relatively slow and inefficient. For example, it takes about a month for the ectopic expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) to fully reprogram human somatic cells to pluripotency. Furthermore, recent studies indicate that there is an initial stochastic phase, whereby random cells in the converting population begin to express a few genes of the new fate, followed by a so-called deterministic phase, whereby activation of a network for the new fate leads to homogeneous changes in gene expression patterns within a subset of the cell population. We recently mapped the initial interactions between OSKM factors and the human genome during the first 48 h of human fibroblast conversion to pluripotency. Unlike that reported in ES and iPS cells, distal enhancer sites in closed chromatin dominate the initial O, S, K and M binding distribution, showing that promoter occupancy is a later ...
INTRODUCTION: We recently isolated a cardiac population of stromal cells (CMSC) that exhibited tissue-specific properties, revealing higher competence for differentiation toward myocardial and vascular lineages than their syngeneic bone marrow counterpart. Despite their plasticity, CMSC did not spontaneously exhibit cardiac stem cell markers, including c-Kit and MDR-1. Since serum and epigenetic drugs, e.g. nitric oxide (NO), retinoic acid (RA), and phenyl butyrate (PB), can modify cell fate and induce functional reprogramming, the aim of the present work was to design an epigenetically-based in vitro strategy to enrich CMSC in a population of putative cardiovascular stem cells.. METHODS AND RESULTS: After a round of expansion in DMEM and 20% fetal bovine serum (FBS), CMSC were exposed, from 3 to 7 days, to low serum (5% FBS) either in the presence or in the absence of a defined "epigenetic cocktail" (EpiC) made of 5 uM ATRA, 5 uM PB and 200 uM DETA/NO. Different parameters were evaluated to ...
Chinese researchers have devised a new technique for reprogramming cells from human urine into immature brain cells that can form multiple types of functioning neurons and glial cells. The technique, published today in the journal Nature Methods, could prove useful for studying the cellular mechanisms of neurodegenerative conditions such as Alzheimers and Parkinsons and for testing the effects of new drugs that are being developed to treat them.. Stem cells offer the hope of treating these debilitating diseases, but obtaining them from human embryos poses an ethical dilemma. We now know that cells taken from the adult human body can be made to revert to a stem cell-like state and then transformed into virtually any other type of cell. This typically involves using genetically engineered viruses that shuttle control genes into the nucleus and inserts them into the chromosomes, whereupon they activate genes that make them pluripotent, or able to re-differentiate into another type of cell.. In ...
Researchers have modeled the development of neurons in some autism patients, offering what they say is a new understanding of the condition.
Oncotarget | https://doi.org/10.18632/oncotarget.11810 Dingqing Feng, Keqin Yan, Ying Zhou, Haiyan Liang, Jing Liang, Weidong Zhao, Zhongjun Dong, Bin Ling
செமினி நுண்மங்கள் தனது நகலாக்கத்திற்கு பயிர் பொறிகளை (machinery) பயன்படுத்துகின்றன. இவை சில மரபணுவை வெளிபடுத்தவதோடு அல்லாமல், அவற்றைக் கொண்டு மிக நேர்த்தியாக பயிர்களின் மரபணுவை பயன்படுத்தி பல்கி பெருகுகின்றன. மேலும் நுண்மங்களின் மரபணு முதிர்ந்த இலைகளின் உயிரணுவில் செயலற்ற மூலக்கூற்று நிகழ்வினை , மறு- நிகழ்வு அல்லது மறு-வினைக்கு (cell reprogramming) உட்படுத்தி நகலாக்கம் ...
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