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JAMA Jan 2017
Topics: Adult Stem Cells; Cell Differentiation; Embryonic Stem Cells; Hematopoietic Stem Cells; Humans; Marketing of Health Services; Pluripotent Stem Cells; Quackery; Stem Cell Transplantation; Stem Cells
PubMed: 28114555
DOI: 10.1001/jama.2016.17822 -
Cell Stem Cell Aug 2023TET2 is recurrently mutated in acute myeloid leukemia (AML) and its deficiency promotes leukemogenesis (driven by aggressive oncogenic mutations) and enhances leukemia...
TET2 is recurrently mutated in acute myeloid leukemia (AML) and its deficiency promotes leukemogenesis (driven by aggressive oncogenic mutations) and enhances leukemia stem cell (LSC) self-renewal. However, the underlying cellular/molecular mechanisms have yet to be fully understood. Here, we show that Tet2 deficiency significantly facilitates leukemogenesis in various AML models (mediated by aggressive or less aggressive mutations) through promoting homing of LSCs into bone marrow (BM) niche to increase their self-renewal/proliferation. TET2 deficiency in AML blast cells increases expression of Tetraspanin 13 (TSPAN13) and thereby activates the CXCR4/CXCL12 signaling, leading to increased homing/migration of LSCs into BM niche. Mechanistically, TET2 deficiency results in the accumulation of methyl-5-cytosine (mC) modification in TSPAN13 mRNA; YBX1 specifically recognizes the mC modification and increases the stability and expression of TSPAN13 transcripts. Collectively, our studies reveal the functional importance of TET2 in leukemogenesis, leukemic blast cell migration/homing, and LSC self-renewal as an mRNA mC demethylase.
Topics: Humans; RNA, Messenger; Leukemia, Myeloid, Acute; Bone Marrow; Carcinogenesis; Stem Cells; Demethylation; Neoplastic Stem Cells; Tetraspanins; DNA-Binding Proteins; Dioxygenases
PubMed: 37541212
DOI: 10.1016/j.stem.2023.07.001 -
Progress in Molecular Biology and... 2023Stem cells have self-renewal capability and can proliferate and differentiate into a variety of functionally active cells that can serve in various tissues and organs.... (Review)
Review
Stem cells have self-renewal capability and can proliferate and differentiate into a variety of functionally active cells that can serve in various tissues and organs. This review discusses the history, definition, and classification of stem cells. Human pluripotent stem cells (hPSCs) mainly include embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Embryonic stem cells are derived from the inner cell mass of the embryo. Induced pluripotent stem cells are derived from reprogramming somatic cells. Pluripotent stem cells have the ability to differentiate into cells derived from all three germ layers (endoderm, mesoderm, and ectoderm). Adult stem cells can be multipotent or unipotent and can produce tissue-specific terminally differentiated cells. Stem cells can be used in cell therapy to replace and regenerate damaged tissues or organs.
Topics: Adult; Humans; Embryonic Stem Cells; Pluripotent Stem Cells; Adult Stem Cells; Induced Pluripotent Stem Cells; Cell Differentiation
PubMed: 37678976
DOI: 10.1016/bs.pmbts.2023.02.012 -
Cells Mar 2021The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].
The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].
Topics: Adult Stem Cells; Cell- and Tissue-Based Therapy; Homeostasis; Humans; Neoplastic Stem Cells; Organoids; Radiation; Stem Cells
PubMed: 33808269
DOI: 10.3390/cells10040760 -
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 -
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 -
Cellular and Molecular Life Sciences :... May 2015Autophagy is an evolutionarily conserved process that degrades cytoplasmic components, thus contributing to cell survival and tissue homeostasis. Recent studies have... (Review)
Review
Autophagy is an evolutionarily conserved process that degrades cytoplasmic components, thus contributing to cell survival and tissue homeostasis. Recent studies have demonstrated that autophagy maintains stem cells in relatively undifferentiated states (stemness) and also contributes to differentiation processes. Autophagy likewise plays a crucial role in somatic cell reprogramming, a finely regulated process that resets differentiated cells to a pluripotent state and that requires comprehensive alterations in transcriptional activities and epigenetic signatures. Autophagy assists in manifesting the functional consequences that arise from these alterations by modifying cellular protein expression profiles. The role of autophagy appears to be particularly relevant for early phases of cell reprogramming during the generation of induced pluripotent stems cells (iPSCs). In this review, we provide an overview of the core molecular machinery that constitutes the autophagic degradation system, describe the roles of autophagy in maintenance, self-renewal, and differentiation of stem cells, and discuss the autophagic process and its regulation during cell reprogramming.
Topics: Animals; Autophagy; Cell Differentiation; Cell Proliferation; Cellular Reprogramming; Humans; Induced Pluripotent Stem Cells; Stem Cells
PubMed: 25572296
DOI: 10.1007/s00018-014-1829-3 -
Oncogene Oct 2001Despite intensive molecular biology investigations over the past 10 years, and an important breakthrough on how PML-RARalpha, the fusion protein resulting from t(15;17),... (Review)
Review
Orchestration of multiple arrays of signal cross-talk and combinatorial interactions for maturation and cell death: another vision of t(15;17) preleukemic blast and APL-cell maturation.
Despite intensive molecular biology investigations over the past 10 years, and an important breakthrough on how PML-RARalpha, the fusion protein resulting from t(15;17), can alter RARalpha and PML functions, no definitive views on how leukemia is generated and by what mechanism(s) the normal phenotype is restored, are yet available. 'Resistances' to pharmacological levels of all-trans-retinoic acid (ATRA) have been observed in experimental in vivo and in vitro models. In this review, we emphasize the key role played by signal cross-talk for both normal and neoplastic hemopoiesis. After an overview of reported experimental data on APL-cell maturation and apoptosis, we apply our current knowledge on signaling pathways to underline those which might generate signal cross-talks. The design of biological models suitable to decipher the integration of signal cross-talks at the transcriptional level should be our first priority today, to generate some realistic therapeutic approaches After 'Ten Years of Molecular APL', we still know very little about how the disease develops and how effective medicines work.
Topics: Apoptosis; Bone Marrow Cells; Cell Differentiation; Cell Transformation, Neoplastic; Disease Progression; Hematopoiesis; Humans; Leukemia, Promyelocytic, Acute; Neoplasm Proteins; Oncogene Proteins, Fusion; Receptor Cross-Talk; Receptors, Retinoic Acid; Retinoid X Receptors; Signal Transduction; Stem Cells; Transcription Factors; Translocation, Genetic
PubMed: 11704845
DOI: 10.1038/sj.onc.1204760 -
Trends in Neurosciences Jul 2003The numbers, types and locations of stem cells in the nervous system have been the subject of much discussion. This review summarizes data on the types of stem cell... (Review)
Review
The numbers, types and locations of stem cells in the nervous system have been the subject of much discussion. This review summarizes data on the types of stem cell present at different stages of development and in the adult brain, and the markers suggested to distinguish between the various possibilities that have been reported. We present evidence that more than one class of stem cell is present in the developing and adult nervous systems, and that it might be possible to distinguish between stem-cell populations and to localize the cell of origin of a particular neurosphere, based on markers that persist in culture and by using universal stem-cell markers prospectively to identify stem cells in vivo.
Topics: Animals; Biomarkers; Brain; Nervous System; Stem Cells
PubMed: 12850431
DOI: 10.1016/S0166-2236(03)00169-3