• Induced totipotent cells can be obtained by reprogramming somatic cells with somatic-cell nuclear transfer (SCNT). (wikipedia.org)
  • Analysis of the effectiveness of caffeine and MG132 for improving somatic cell nuclear transfer (SCNT) technology using cryopreserved eggs showed that supplementation did not improve the blastocyst formation rate of cloned mouse eggs. (molcells.org)
  • Although exciting results have been achieved by means of somatic cell nuclear transfer, cell fusion, and culture-induced reprogramming [ 1 ], these procedures are technically demanding and inefficient and therefore unlikely to become a common approach for producing patient-specific pluripotent cells. (biomedcentral.com)
  • In mouse, only epiblast cells can be directly converted into cultured pluripotent embryonic stem cells, capable of forming all adult cell types. (bioone.org)
  • They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo. (wikipedia.org)
  • They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo. (wikipedia.org)
  • Mouse ES cells have been widely utilized as an in vitro model to study cardiogenesis, as cardiomyocytes were found to spontaneously differentiate from ES cells after withdrawal of LIF (leukemia inhibitory factor), which functions to maintain the pluripotency of undifferentiated mouse ES cells [ 2 - 4 ]. (biomedcentral.com)
  • We discuss what is known about the distinct metabolic states captured in vitro by the 2-cell-like, naïve, blastocyst-like, formative, and primed states of pluripotency. (conditionmed.org)
  • 2019). Akin to the dynamic nutrient requirements of the developing embryo, discrete in vitro cell states have distinct metabolic profiles (Zhou et al. (conditionmed.org)
  • It is only through understanding embryonic metabolism and development that we can derive and maintain different in vitro stem cell states for disease modeling and therapies. (conditionmed.org)
  • In vitro fertilized (IVF) embryos were cultured in the presence of dimethyl sulfoxide or inhibitors of MAP2K (0.4 μM PD0325901) and GSK3 (3 μM CHIR99021) from the zygote (Day 1) stage. (bioone.org)
  • Monkeys have served as one of the most valuable models for understanding DNA methylation dynamics during early embryogenesis in human due to their similarities in genetics and early embryonic development 17 , 18 . (nature.com)
  • Furthermore, due to ethical and legal concerns, very limited techniques can be applied to human embryos to validate some of significant conclusions drawn from descriptive studies regarding human embryonic development. (nature.com)
  • The process involves sucking out the nucleus of a somatic (body) cell and injecting it into an oocyte that has had its nucleus removed Using an approach based on the protocol outlined by Tachibana et al. (wikipedia.org)
  • In 1-cell and 2-cell embryos Dnmt1s is derived from the oocyte, whereas from the 2-cell stage onward the embryo starts to synthesize its own Dnmt1s 8 . (nature.com)
  • Another drawback of oocyte vitrification is diminished developmental potential because of the decreased quality of embryos after warming. (molcells.org)
  • hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells. (wikipedia.org)
  • Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. (nature.com)
  • However, robust and large-scale genome-wide reprogramming of DNA methylome occurs during two critical developmental processes: (1) development of primordial germ cells and (2) pre-implantation embryogenesis. (nature.com)
  • Although the genome-wide DNA demethylation is believed to be a hallmark of mammalian embryogenesis, previous study also indicated that the somatic form of dnmt1 ( dnmt1s ) is actually expressed at each stage of pre-implantation embryos and plays a role in the maintenance of DNA imprinting 8 . (nature.com)
  • In addition, we summarize the recent direct reprogramming of cardiomyocytes from fibroblast cells, which provides another method for potential heart disease therapy. (biomedcentral.com)
  • In this review, we summarize the history of interspecies chimerism in various animal models to find hints for BC application and describe the challenges and prospects of utilizing BC for human organ generation. (frontiersin.org)
  • Here, we summarize current reprogramming methodologies with a focus on the production of transgene-free or genetically unmanipulated iPSCs and highlight important technical details that ultimately may influence the biological properties of pluripotent stem cells. (biomedcentral.com)
  • They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent - iMSC, also called an induced multipotent progenitor cell - iMPC) or unipotent - (iUSC) according to their developmental potential and degree of dedifferentiation. (wikipedia.org)
  • Up to the 2-cell embryo, blastomeres remain totipotent (Garner and McLaren, 1974). (conditionmed.org)
  • In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. (frontiersin.org)
  • In the mouse, a transporting epithelium is established around the 8-16-cell stage through a process known as compaction where cell definition is lost and the outer cells of the embryo form tight junctions, giving rise to the blastocyst. (conditionmed.org)
  • The blastocyst comprises the inner cell mass (ICM), which gives rise to the three primary germ layers and consequently the fetus, and the trophectoderm (TE), which gives rise to the extraembryonic and placental tissue. (conditionmed.org)
  • Compared to vehicle controls, 2i conditions increased the abundance of cumulus cells in bovine IVF cultures, which compromised blastocyst formation. (bioone.org)
  • Following cumulus removal, 2i accelerated blastocyst development and increased inner cell mass (ICM) and trophoblast cell numbers by 30% and 27%, respectively. (bioone.org)
  • The differentiated ES cell cultures are heterogeneous and contain undifferentiated ES cells, which could result in teratoma formation after transplantation into the host. (biomedcentral.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)
  • In addition, as the genetic identity of the donor egg from which the ESCs are derived most likely will differ from that of potential recipients, patients who receive ESC-derived cells or tissues may face the same complications that result from organ transplantation (for example, immunorejection, graft-versus-host disease, and need for immunosuppression). (biomedcentral.com)
  • Ideally, iPSC-based therapies in the future will rely on the isolation of skin fibroblasts or keratinocytes, their reprogramming into iPSCs, and the correction of the genetic defect followed by differentiation into the desired cell type and transplantation. (biomedcentral.com)
  • Although it is possible to culture structures derived from human blastocysts ex vivo, these cultures do not recapitulate the events and structural organization of the in vivo embryos 6 ( Supplementary Information ). (nature.com)
  • However, the cell numbers in blastocysts did not differ among groups. (molcells.org)
  • 2008). Historically, this concept is highlighted by the experi- factors are key intrinsic regulators of these fate decisions and mental phenomenon of lineage reprogramming, for example, that fate choice involves modulating networks of transcription by the conversion of fibroblasts to muscles cells following trans- factors. (lu.se)
  • In 2006, a major breakthrough was reported in Japan by Takahashi and Yamanaka, who described the generation of induced pluripotent stem cells (iPSCs) from mouse fibroblasts via over expression of defined transcription factors [ 2 ]. (biomedcentral.com)
  • In cultured primary fibroblasts and cancer cells, the chemotherapeutic drug doxorubicin causes mtDNA damage and release, which leads to cGAS STING dependent ISG activation. (regenerativemedicine.net)
  • Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. (nature.com)
  • These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. (nature.com)
  • Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells. (wikipedia.org)
  • This meant that the cells can change their differentiation pathway. (wikipedia.org)
  • In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. (wikipedia.org)
  • The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation. (wikipedia.org)
  • In this review, we describe the cardiac differentiation from ES cells, iPS cells, and the current progress of using iPS cell-derived cardiomyocytes for heart disease modeling and for the development of therapeutic strategies. (biomedcentral.com)
  • Stem and progenitor cell populations are often heterogeneous, which may reflect stem cell subsets that express subtly different properties, including different propensities for lineage selection upon differentiation, yet remain able to interconvert. (lu.se)
  • A key challenge is to understand how state, but must also afford flexibility in cell-fate choice to permit the different cell-fate options confronting stem and progenitor cell-type diversification and differentiation in response to cells are selected and coordinated such that adoption of a given intrinsic cues or extrinsic signals. (lu.se)
  • Evidence the fate of stem cells has broad ramifications for biomedical suggests that during development or differentiation, cells make science from elucidating the causes of cancer to the use of very precise transitions between apparently stable ``network stem cells in regenerative medicine. (lu.se)
  • To establish protocols for the safe and efficient differentiation of healthy cells for therapies, we must develop a better understanding of the dynamic continuum of metabolic states that span pluripotency and differentiation, and how to influence them. (conditionmed.org)
  • Dazl can regulate the expression, transport and localization of target mRNAs of proteins which control the differentiation, growth and maturation of germ cells. (ijbs.com)
  • DAZ family proteins are found almost exclusively in germ cells in distant animal species. (ijbs.com)
  • Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. (ijbs.com)
  • DAZ family proteins are located in the nucleus and/or in the cytoplasm of male and female germ cells at different developmental stages throughout the gametogenesis. (ijbs.com)
  • Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking 1 , 2 . (nature.com)
  • Much of this process relies on the morphogenesis of the extra-embryonic tissues and the effect this has on the organization of embryonic cells. (nature.com)
  • Some of these concerns, such as ensuring the welfare of research animals and obtaining appropriate consent for the use of human tissues, also apply to many other areas of research, but may require special consideration for research with human neural organoids, cell transplants, and chimeras. (nationalacademies.org)
  • Given the complexity of the human brain and the particularly human nature of many key symptoms of these disorders, especially psychiatric disorders, animal and cell culture models of the types currently used to investigate diseases of other organs and tissues are valuable but inadequate. (nationalacademies.org)
  • Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
  • Cryopreservation of mammalian oocytes has been successfully applied for long-term storage of surplus eggs in mammalian assisted reproductive technology (ART), including in humans. (molcells.org)
  • Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. (atlas-d2k.org)
  • These advances have provided new insights into the molecular mechanisms of reprogramming and promise to accelerate the clinical translation of iPSC technology. (biomedcentral.com)
  • In Enhancing Evolution, leading bioethicist John Harris dismantles objections to genetic engineering, stem-cell research, designer babies, and cloning and makes an ethical case for biotechnology that is both forthright and rigorous. (philpapers.org)
  • Human enhancement, Harris argues, is a good thing--good morally, good for individuals, good as social policy, and good for a genetic heritage that needs serious improvement. (philpapers.org)
  • The nature of the stem cell substates and their relationship to commitment to differ- entiate and lineage selection can be elucidated in terms of a landscape picture in which stable states can be defined mathematically as attractors. (lu.se)
  • This requirement strongly limits the number of solutions or entiation and lineage-specification, programmed cell death, and ``states'' for the system. (lu.se)
  • Similarly, GATA-1 has been shown to induce lineage switching expression values even if, for simplicity, we assume only ``on'' of committed cells in hematopoiesis, first in cell lines (Kulessa and ``off'' states for each gene. (lu.se)
  • We discuss these properties with examples both from the hematopoietic and embryonic stem cell (ESC) systems. (lu.se)
  • After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. (wikipedia.org)
  • Specifically, human iPS cells could be utilized to generate patient-specific lineages for a variety of translational research. (biomedcentral.com)
  • To varying degrees, these fates also extend to the Such state stability is required in stem and progenitor cells to immediate progeny of stem cells, known as progenitor or support self-renewal and maintenance of the uncommitted transit-amplifying cells. (lu.se)
  • In terminally differentiated cell fate is coupled to appropriate regulation of the alternative cells, transcriptional networks must be stable and irreversible, pathways. (lu.se)
  • The potential use of embryonic stem cells (ESCs) for cell replacement therapies is limited by ethical concerns and the technical hurdles associated with their isolation from human embryos. (biomedcentral.com)
  • The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation 1 . (nature.com)
  • These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days after fertilization (Carnegie stage 6a). (nature.com)
  • This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development. (nature.com)
  • Implantation of the human embryo leads to a number of changes in organization that are essential for gastrulation and future development 1 . (nature.com)
  • and (3) evidence of developmental dynamism relating to ability to progress, in a structurally organized manner, through morphologically characterized developmental milestones of the early post-implantation human embryo following initial aggregate formation 3 . (nature.com)
  • 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)
  • As explained in Chapter 2 , human neural organoids, transplants, and chimeras provide new models for such conditions and may lead to new knowledge about brain development and function, the discovery of disease mechanisms, new therapeutic targets, and better screening of potential new treatments. (nationalacademies.org)
  • However, it is only in the last decade that we have finally come to understand their underlying mechanisms of action in gonadotroph cells. (bioone.org)
  • The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. (wikipedia.org)
  • The developing embryo, from which pluripotent stem cells originate, undergoes a series of dynamic metabolic transitions synchronized to its molecular development. (conditionmed.org)
  • Our project focuses on characterizing and optimizing this approach to improve tubular maturation and cellular function and generating reporter lines for the isolation of specific cell types. (atlas-d2k.org)
  • A main justification for carrying out research, both basic and translational, with human neural organoids, transplants, and chimeras is that it will help in the discovery of new ways to understand and treat neurological and psychiatric disorders, which, as discussed previously, cause immense suffering and for which treatments are ineffective or lacking. (nationalacademies.org)
  • International bi-monthly journal of cell signaling, tissue protection, and translational research. (conditionmed.org)
  • We explore the recently described metabolic surge event that occurs as pluripotency is lost and stem cells commit to differentiate. (conditionmed.org)
  • To circumvent these obstacles, considerable effort has been invested in attempting to derive ESC-like cells by reprogramming somatic cells to an embryonic state. (biomedcentral.com)
  • Several experimental strategies have been developed to derive iPSCs from differentiated somatic cells (summarized in Figure 1 ). (biomedcentral.com)
  • The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. (atlas-d2k.org)
  • Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. (atlas-d2k.org)
  • In order, therefore, to obtain a purified cardiomyocyte population from mouse ES cells, several approaches have been developed. (biomedcentral.com)
  • In this review, we outline current reprogramming approaches developed to improve the safety and efficiency of the method and highlight its critical aspects that may have an impact on the quality of the iPSCs. (biomedcentral.com)
  • Some types of mature, specialized adult cells can naturally revert to stem cells. (wikipedia.org)
  • Embryonic stem (ES) cells are naturally derived from early stage embryos and induced pluripotent stem (iPS) cells are reprogrammed from somatic cells with overexpression of four reprogramming factors, Oct4, Sox2, Klf4 and c-Myc. (biomedcentral.com)
  • In 1924 Hans Spemann and Hilde Mangold demonstrated the key importance of cell-cell inductions during animal development. (wikipedia.org)
  • We therefore decided to investigate comprehensively the global and high-resolution DNA methylation dynamics during early development of a non-human primate (rhesus monkey, Macaca mulatta ). (nature.com)
  • Here, we consider the metabolism of the early embryo through development, and look at the nutrient milieu within the developing stem cell niche. (conditionmed.org)
  • 2020). This places metabolism at the forefront of development and cell state decisions. (conditionmed.org)
  • BACKGROUND: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. (atlas-d2k.org)
  • The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation. (atlas-d2k.org)
  • Both ES cells and iPS cells are pluripotent stem cells with capabilities of indefinite self-renewal and can be differentiated into almost all cell types of the body, which make them valuable for studying early developmental biology, for modeling and as therapy for human diseases. (biomedcentral.com)
  • In the long term, human kidney tissue generated in this way may be used for drug screening, tissue regeneration or cell therapy. (atlas-d2k.org)
  • Research involving human neural organoids, transplants, and chimeras has an ultimate goal of preventing and treating the great suffering caused by serious neurological and psychiatric conditions for which no effective treatment is available. (nationalacademies.org)
  • One such concern is the possibility of altering the capacities or consciousness of a research animal in ways that may blur the lines between human beings and nonhuman animals. (nationalacademies.org)
  • For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. (wikipedia.org)
  • In reality, gene somatic cells to a pluripotent cell state by a handful of transcrip- expression is graded, making the potential gene expression tion factors (Takahashi and Yamanaka, 2006). (lu.se)
  • DAZ (Deleted in Azoospermia) family genes are important fertility factors in many animals including humans. (ijbs.com)
  • Direct reprogramming was originally achieved by retroviral transduction of transcription factors. (biomedcentral.com)
  • Cliff and Dalton, 2017), with nutrients capable of inducing and maintaining alternate cell states (Shyh-Chang et al. (conditionmed.org)
  • However, this technology also may have several limitations, such as the risk of contamination by external pathogens because of direct contact with liquid nitrogen and increased cell toxicity due to high CPA concentrations. (molcells.org)
  • Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs) 3 . (nature.com)
  • Mouse ES cell-derived EBs were dissociated using collagenase, followed with a modified procedure by Isenberg and Klockner in 1982 to prepare the calcium-tolerant ventricular myocytes [ 18 ]. (biomedcentral.com)
  • However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. (atlas-d2k.org)
  • The biological properties and clinical potential of stem cells elicit that are generated must not be unduly sensitive to small fluctu- continued scientific, commercial, and public interest. (lu.se)
  • Ethical issues common to human neural organoids, transplants, and chimeras include (1) the ethical value of relieving human suffering and disease, (2) concerns about encroachment on divine roles, and (3) ethical issues related to human donors of biological materials. (nationalacademies.org)
  • Chapter 2 presents the science behind these models and describes the challenges of measuring and monitoring such characteristics and capacities in human neural organoids, transplants, and chimeras. (nationalacademies.org)
  • neural organoids, transplants, and chimeras, and then at issues specific to human neural transplants and chimeras or to neural organoids. (nationalacademies.org)
  • One example is the transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. (wikipedia.org)
  • ES cells were aggregated into three-dimensional structures, termed embryoid bodies (EBs), and suspended in media containing fetal calf serum. (biomedcentral.com)
  • The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. (atlas-d2k.org)