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ELife Mar 2019The characteristic properties of stem cells - notably their ability to self-renew and to differentiate - have meant that they have traditionally been viewed as distinct...
The characteristic properties of stem cells - notably their ability to self-renew and to differentiate - have meant that they have traditionally been viewed as distinct from most other types of cells. However, recent research has blurred the line between stem cells and other cells by showing that the former display a range of behaviors in different tissues and at different stages of development. Here, we use the tools of metaphysics to describe a classification scheme for stem cells, and to highlight what their inherent diversity means for cancer treatment.
Topics: Phenotype; Stem Cells
PubMed: 30864951
DOI: 10.7554/eLife.46563 -
Acta Biochimica Polonica 2015Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent... (Review)
Review
Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology.
Topics: Adult; Adult Stem Cells; Animals; Cell Lineage; Embryonic Stem Cells; Gene Expression Profiling; Gene Expression Regulation; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Regenerative Medicine; Stem Cell Transplantation; Stem Cells
PubMed: 26200199
DOI: 10.18388/abp.2015_1023 -
Cell Stem Cell May 2014The liver is a central organ for homeostasis with unique regenerative capacities. Mature hepatocytes possess a remarkable capacity to proliferate upon injury,... (Review)
Review
The liver is a central organ for homeostasis with unique regenerative capacities. Mature hepatocytes possess a remarkable capacity to proliferate upon injury, challenging efforts to discern the role of adult liver stem cells in this process. In contrast, stem/progenitor cells in the developing liver have been extensively characterized, and these investigations have informed efforts to produce functional hepatocytes in vitro for cell therapy and drug screening. In this Review, we describe recent advances in the characterization of liver stem cells and discuss evidence supporting and refuting whether self-renewable and bipotential liver stem cells exist in development, homeostasis, regeneration, and disease.
Topics: Animals; Homeostasis; Humans; Liver; Regeneration; Stem Cells
PubMed: 24792114
DOI: 10.1016/j.stem.2014.04.010 -
Cancer Cell Mar 2018The lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A...
The lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A inhibitor that induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML. ORY-1001 exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of an AML xenograft model, and extends survival in a mouse PDX (patient-derived xenograft) model of T cell acute leukemia. Surrogate pharmacodynamic biomarkers developed based on expression changes in leukemia cell lines were translated to samples from patients treated with ORY-1001. ORY-1001 is a selective KDM1A inhibitor in clinical trials and is currently being evaluated in patients with leukemia and solid tumors.
Topics: Animals; Apoptosis; Cell Differentiation; Cell Line, Tumor; Disease Models, Animal; Histone Demethylases; Humans; Leukemia, Myeloid, Acute; Mice; Stem Cells
PubMed: 29502954
DOI: 10.1016/j.ccell.2018.02.002 -
Cell Stem Cell Jul 2015Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly...
Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.
Topics: Animals; Cell Differentiation; Cell Lineage; Cellular Reprogramming; Gene Expression; Hematopoiesis; Hematopoietic Stem Cells; Lymphoid Progenitor Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; Multipotent Stem Cells; Myeloid Progenitor Cells; Regeneration
PubMed: 26095048
DOI: 10.1016/j.stem.2015.05.003 -
Stem Cell Research May 2014Despite advances in the field of somatic cell reprogramming, an understanding and exploration of the underlying mechanisms governing this process are only recently... (Review)
Review
Despite advances in the field of somatic cell reprogramming, an understanding and exploration of the underlying mechanisms governing this process are only recently emerging. It is now increasingly apparent that key sequential events correlate with the reprogramming process; a process previously thought to be random and unpredictable is now looking, to a greater extent, defined and controlled. Herein, we will review the key cellular and molecular events associated with the reprogramming process, giving an integrative and conciliatory view of the different studies addressing the mechanism of nuclear reprogramming.
Topics: Animals; Cell Differentiation; Cellular Reprogramming; Humans; Stem Cells
PubMed: 24735951
DOI: 10.1016/j.scr.2014.03.007 -
Biochemistry. Biokhimiia Mar 2019Perhaps there is no more intriguing topic in modern biology than stem cells. The growing interest in stem cells is dictated by the ability of stem cells to both...
Perhaps there is no more intriguing topic in modern biology than stem cells. The growing interest in stem cells is dictated by the ability of stem cells to both self-renew and differentiate, at least into several type cells. If we learn to influence these properties or reproduce them in vitro, it will be possible to effectively use stem cells or their differentiated derivatives in medicine. Fundamental knowledge of mechanisms of the self-maintenance and differentiation of stem cells is important for understanding a variety of processes - from embryogenesis to aging and oncogenic transformation. The purpose of this issue is to introduce readers to different areas in research on mammalian stem cells, including human stem cells. In the issue both review articles and research papers are presented, and the authors hope that they will be of interest for biochemists, cell biologists, and specialists in the field of biomedicine.
Topics: Animals; Cell Differentiation; Humans; Stem Cells
PubMed: 31221057
DOI: 10.1134/S0006297919030015 -
Current Biology : CB Sep 2016Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for... (Review)
Review
Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration and the end of cancer have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being. Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. Surprisingly, the cellular and molecular design of these systems is remarkably similar, even across diverse species. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation. In this minireview, we introduce the basic features of the three major plant stem cell systems building on these facts, highlight their modular design at the level of cellular layout and regulatory underpinnings and briefly compare them with their animal counterparts.
Topics: Plant Cells; Stem Cells
PubMed: 27623267
DOI: 10.1016/j.cub.2016.07.070 -
Cell Research Jan 2012
Topics: Cell Differentiation; Gene Expression Regulation; Humans; Immunity, Cellular; Neoplasms; Signal Transduction; Stem Cells
PubMed: 22218108
DOI: 10.1038/cr.2012.7 -
Biomolecular Concepts Mar 2015Stem cells are identified classically by an in vivo transplantation assay plus additional characterization, such as marker analysis, linage-tracing and in vitro/ex vivo... (Review)
Review
Stem cells are identified classically by an in vivo transplantation assay plus additional characterization, such as marker analysis, linage-tracing and in vitro/ex vivo differentiation assays. Stem cell lines have been derived, in vitro, from adult tissues, the inner cell mass (ICM), epiblast, and male germ stem cells, providing intriguing insight into stem cell biology, plasticity, heterogeneity, metastable state, and the pivotal point at which stem cells irreversibly differentiate to non-stem cells. During the past decade, strategies for manipulating cell fate have revolutionized our understanding about the basic concept of cell differentiation: stem cell lines can be established by introducing transcription factors, as with the case for iPSCs, revealing some of the molecular interplay of key factors during the course of phenotypic changes. In addition to de-differentiation approaches for establishing stem cells, another method has been developed whereby induced expression of certain transcription factors and/or micro RNAs artificially converts differentiated cells from one committed lineage to another; notably, these cells need not transit through a stem/progenitor state. The molecular cues guiding such cell fate conversion and reprogramming remain largely unknown. As differentiation and de-differentiation are directly linked to epigenetic changes, we overview cell fate decisions, and associated gene and epigenetic regulations.
Topics: Animals; Cell Differentiation; Embryonic Development; Epigenesis, Genetic; Humans; Stem Cells
PubMed: 25720089
DOI: 10.1515/bmc-2014-0036