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Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming.International Journal of Molecular... Jun 2021Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body... (Review)
Review
Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.
Topics: Cell Differentiation; Cell Proliferation; Cellular Reprogramming; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Single-Cell Analysis; Transcriptome
PubMed: 34206025
DOI: 10.3390/ijms22115988 -
International Journal of Molecular... Aug 2019Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the... (Review)
Review
Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the contributions of astrocytes in human diseases. Here we review human iPSC-based models for neurological disorders associated with human astrocytes and discuss the points of each model.
Topics: Animals; Astrocytes; Biomarkers; Cell Differentiation; Disease Susceptibility; Humans; Induced Pluripotent Stem Cells; Models, Biological; Nervous System Diseases; Neuroglia; Phenotype; Pluripotent Stem Cells
PubMed: 31398826
DOI: 10.3390/ijms20163862 -
Cell Stem Cell Nov 2015Embryonic pluripotency can be recapitulated in vitro by a spectrum of pluripotent stem cell states stabilized with different culture conditions. Their distinct... (Review)
Review
Embryonic pluripotency can be recapitulated in vitro by a spectrum of pluripotent stem cell states stabilized with different culture conditions. Their distinct spatiotemporal characteristics provide an unprecedented tool for the study of early human development. The newly unveiled ability of some stem cell types for crossing xeno-barriers will facilitate the generation of interspecies chimeric embryos from distant species, including humans. When combined with efficient zygote genome editing technologies, xenogeneic human pluripotent stem cells may also open new frontiers for regenerative medicine applications, including the possibility of generating human organs in animals via interspecies chimeric complementation.
Topics: Animals; Cell Culture Techniques; Chimera; Humans; Mice; Pluripotent Stem Cells
PubMed: 26544113
DOI: 10.1016/j.stem.2015.10.009 -
Annual Review of Pharmacology and... 2013The liver is a fascinating organ and performs a wide range of functions necessary for life. Because the hepatocyte is the major functional cell type found in the liver,... (Review)
Review
The liver is a fascinating organ and performs a wide range of functions necessary for life. Because the hepatocyte is the major functional cell type found in the liver, it is important that we better understand its role in health and disease. Functional hepatocytes have been derived from many sources, including human stem cell populations. These models offer new opportunities to further our understanding of human liver biology from diverse genotypes and, in the future, to facilitate the development of novel medicines or cell-based therapies. This review discusses limitations in current cell-based models and the advantages offered by pluripotent stem cell-derived hepatocytes.
Topics: Animals; Hepatocytes; Humans; Liver; Pluripotent Stem Cells
PubMed: 23294308
DOI: 10.1146/annurev-pharmtox-011112-140306 -
Cell Apr 2021Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a...
Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a promising strategy for various regenerative medicine applications, including the generation of organs and tissues for transplantation. Studies using mouse and pig embryos suggest that hPSCs do not robustly contribute to chimera formation in species evolutionarily distant to humans. We studied the chimeric competency of human extended pluripotent stem cells (hEPSCs) in cynomolgus monkey (Macaca fascicularis) embryos cultured ex vivo. We demonstrate that hEPSCs survived, proliferated, and generated several peri- and early post-implantation cell lineages inside monkey embryos. We also uncovered signaling events underlying interspecific crosstalk that may help shape the unique developmental trajectories of human and monkey cells within chimeric embryos. These results may help to better understand early human development and primate evolution and develop strategies to improve human chimerism in evolutionarily distant species.
Topics: Animals; Blastocyst; Cell Differentiation; Cell Lineage; Cells, Cultured; Chimerism; Embryo, Mammalian; Female; Humans; Macaca fascicularis; Pluripotent Stem Cells; RNA-Seq; Single-Cell Analysis; Transcriptome
PubMed: 33861963
DOI: 10.1016/j.cell.2021.03.020 -
Stem Cells Translational Medicine May 2014Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has... (Review)
Review
Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has traditionally relied on pharmacotherapy, exemplified by insulin replacement to target peripheral actions of the hormone. With growing understanding of the pathogenesis of diabetic disease, alternative approaches aiming at repair and restoration of failing β-cell function are increasingly considered as complements to current diabetes therapy regimens. To this end, emphasis is placed on transplantation of exogenous pancreas/islets or artificial islets, enhanced proliferation and maturation of endogenous β cells, prevention of β-cell loss, or fortified renewal of β-like-cell populations from stem cell pools and non-β-cell sources. In light of emerging clinical experiences with human embryonic stem cells and approval of the first in-human trial with induced pluripotent stem cells, in this study we highlight advances in β-cell regeneration strategies with a focus on pluripotent stem cell platforms in the context of translational applications.
Topics: Animals; Diabetes Mellitus; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Insulin-Secreting Cells; Regenerative Medicine; Stem Cell Transplantation
PubMed: 24646490
DOI: 10.5966/sctm.2013-0184 -
Cellular and Molecular Life Sciences :... Jul 2017Despite the recent promising results of clinical trials using human pluripotent stem cell (hPSC)-based cell therapies for age-related macular degeneration (AMD), the... (Review)
Review
Despite the recent promising results of clinical trials using human pluripotent stem cell (hPSC)-based cell therapies for age-related macular degeneration (AMD), the risk of teratoma formation resulting from residual undifferentiated hPSCs remains a serious and critical hurdle for broader clinical implementation. To mitigate the tumorigenic risk of hPSC-based cell therapy, a variety of approaches have been examined to ablate the undifferentiated hPSCs based on the unique molecular properties of hPSCs. In the present review, we offer a brief overview of recent attempts at selective elimination of undifferentiated hPSCs to decrease the risk of teratoma formation in hPSC-based cell therapy.
Topics: Animals; Cell Death; Genes, Transgenic, Suicide; Humans; MicroRNAs; Mitochondria; Pluripotent Stem Cells; Small Molecule Libraries; Stem Cell Transplantation
PubMed: 28246701
DOI: 10.1007/s00018-017-2486-0 -
Current Opinion in Cell Biology Dec 2015Human induced pluripotent stem cells (hiPSCs) can yield unlimited numbers of patient-specific cells of any type and may be an important tool in efforts to overcome... (Review)
Review
Human induced pluripotent stem cells (hiPSCs) can yield unlimited numbers of patient-specific cells of any type and may be an important tool in efforts to overcome current shortcomings in biomedical research. In vitro disease models based on the use of hiPSCs have been proposed for various applications. Those include drug discovery and validation, efficacy, safety and toxicity assays, the elucidation of previously unknown disease mechanisms, the enhancement of animal based assays, the promise of conducting clinical trials in the dish and the identification of cell types and stages suitable for cell replacement therapies. Here, we provide an overview of the current state of hiPSC-based disease modeling and discuss recent progress and remaining challenges on the road to realizing the full potential of this novel technology.
Topics: Animals; Cell Differentiation; Cellular Reprogramming; Drug Discovery; Humans; Models, Biological; Pluripotent Stem Cells; Stress, Physiological
PubMed: 26629748
DOI: 10.1016/j.ceb.2015.10.008 -
Regenerative Medicine Jul 2012Diabetes mellitus, which affects 346 million people, is one of the leading causes of death worldwide. Pancreatic β-cells, existing in the islets of Langerhans, play... (Review)
Review
Diabetes mellitus, which affects 346 million people, is one of the leading causes of death worldwide. Pancreatic β-cells, existing in the islets of Langerhans, play central roles in the progression of diabetes. An efficient strategy to produce functional pancreatic β-cells is important for both transplantation therapy and disease modeling of diabetes. Human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, provide unlimited starting materials to generate differentiated cells for regenerative studies. Significant progress has been made in human embryonic/induced pluripotent stem cell differentiation in the last several years. However, efficient generation of mature pancreatic β-cells with complete functional capabilities has not yet been accomplished. Here, we review recent successes as well as the technical and theoretical challenges in the use of pluripotent stem cell-derived pancreatic β-cells for disease modeling and replacement therapy of diabetes.
Topics: Animals; Cell Differentiation; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Pluripotent Stem Cells; Regenerative Medicine; Stem Cell Transplantation
PubMed: 22817630
DOI: 10.2217/rme.12.27 -
Cell Stem Cell Dec 2017Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based...
Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based modeling of tissue development, recapitulating these complex configurations from pluripotent stem cells (PSCs) has remained challenging. In this study, we report assembly of kidney organoids that recapitulate embryonic branching morphogenesis. By studying the distinct origins and developmental processes of the ureteric bud, which contains epithelial kidney progenitors that undergo branching morphogenesis and thereby plays a central role in orchestrating organ geometry, and neighboring mesenchymal nephron progenitors, we established a protocol for differential induction of each lineage from mouse and human PSCs. Importantly, reassembled organoids developed the inherent architectures of the embryonic kidney, including the peripheral progenitor niche and internally differentiated nephrons that were interconnected by a ramified ureteric epithelium. This selective induction and reassembly strategy will be a powerful approach to recapitulate organotypic architecture in PSC-derived organoids.
Topics: Animals; Cells, Cultured; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Organogenesis; Pluripotent Stem Cells
PubMed: 29129523
DOI: 10.1016/j.stem.2017.10.011