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Sean J Morrison - One of the best experts on this subject based on the ideXlab platform.
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Adult haematopoietic stem cell Niches
Nature Reviews Immunology, 2017Co-Authors: Genevieve M Crane, Elise Jeffery, Sean J MorrisonAbstract:Recent advances in imaging techniques and genetic tools have rapidly increased our understanding of the Niches that maintain adult haematopoietic stem cells, including the constituent cell types and the factors that directly or indirectly regulate these Niches. Dividing and non-dividing haematopoietic stem cells (HSCs) reside in perivascular Niches that are mainly associated with sinusoidal blood vessels in adult bone marrow and spleen. A subset of HSCs is most closely associated with arterioles. The periarteriolar and perisinusoidal microenvironments differ in terms of the capacity of HSCs to intravasate into the circulation and in terms of their exposure to blood plasma components. Endothelial cells and leptin receptor-expressing, CXC-chemokine ligand 12 (CXCL12)-abundant reticular perivascular stromal cells are the main sources of the stem cell factor (SCF) and CXCL12 required for HSC maintenance in normal young-adult bone marrow. Other perivascular cells, such as Ng2 -CreER^+ periarteriolar cells (which express neural–glial antigen 2), may or may not also synthesize the CXCL12 required for HSC maintenance. Several other cell types — including megakaryocytes, monocytes and macrophages, neurons (specifically, nerve fibres) and Schwann cells — directly or indirectly regulate HSC or niche function through other mechanisms. Extramedullary haematopoiesis in the spleen depends on a perivascular niche that is associated with sinusoids in the red pulp, in which endothelial cells and transcription factor 21-expressing stromal cells are the main sources of SCF and CXCL12. This niche is necessary for the recovery of haematopoiesis from haematopoietic stresses such as blood loss. The vascular and stromal compositions of the bone marrow change during ageing. Stem cell Niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the Niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo , and improved imaging techniques. Together, they have shown that HSC Niches are perivascular in the bone marrow and spleen. Endothelial cells and mesenchymal stromal cells secrete factors that promote HSC maintenance in these Niches, but other cell types also directly or indirectly regulate HSC Niches.
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adult haematopoietic stem cell Niches
Nature Reviews Immunology, 2017Co-Authors: Genevieve M Crane, Elise Jeffery, Sean J MorrisonAbstract:Stem cell Niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the Niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. Together, they have shown that HSC Niches are perivascular in the bone marrow and spleen. Endothelial cells and mesenchymal stromal cells secrete factors that promote HSC maintenance in these Niches, but other cell types also directly or indirectly regulate HSC Niches.
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the bone marrow niche for haematopoietic stem cells
Nature, 2014Co-Authors: Sean J Morrison, David T ScaddenAbstract:Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their Niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
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uncertainty in the Niches that maintain haematopoietic stem cells
Nature Reviews Immunology, 2008Co-Authors: Mark J Kiel, Sean J MorrisonAbstract:Haematopoietic stem cell (HSC) Niches are specialized microenvironments that contain stem cells and regulate their maintenance. Cells at the interface of bone and the bone marrow (the endosteum) contribute to the creation of HSC Niches. It remains uncertain whether this interface itself is a niche, or whether endosteal cells secrete factors that diffuse to nearby Niches. Vascular and/or perivascular cells may also create Niches as many HSCs are observed around sinusoidal blood vessels, and perivascular cells secrete factors that regulate HSC maintenance. Do endosteal and perivascular cells create distinct Niches, or do they contribute to a common niche? We discuss a range of niche models consistent with recent evidence.
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Uncertainty in the Niches that maintain haematopoietic stem cells
Nature Reviews Immunology, 2008Co-Authors: Mark J Kiel, Sean J MorrisonAbstract:Maintenance of haematopoietic stem cells occurs in Niches, but much discussion still surrounds the precise site and nature of these Niches. Here, Mark Kiel and Sean Morrison review various niche models that are compatible with the recent published data. Haematopoietic stem cell (HSC) Niches are specialized microenvironments that contain stem cells and regulate their maintenance. Cells at the interface of bone and the bone marrow (the endosteum) contribute to the creation of HSC Niches. It remains uncertain whether this interface itself is a niche, or whether endosteal cells secrete factors that diffuse to nearby Niches. Vascular and/or perivascular cells may also create Niches as many HSCs are observed around sinusoidal blood vessels, and perivascular cells secrete factors that regulate HSC maintenance. Do endosteal and perivascular cells create distinct Niches, or do they contribute to a common niche? We discuss a range of niche models consistent with recent evidence. Haematopoietic stem cells (HSCs) first arise in close association with intraembryonic and extraembryonic blood vessels, then undergo haematopoiesis in the fetal liver and spleen and later in the bone marrow. The bone marrow is the major site of adult haematopoiesis, but HSCs can also undergo haematopoiesis in the spleen and liver during periods of haematopoietic stress. HSCs Niches are specialized microenvironments that contain and sustain stem cells. The niche includes supporting cells as well as extracellular matrix and soluble factors that are found within the microenvironment. The signals in this microenvironment promote stem-cell survival and self-renewal, but may also regulate migration and differentiation to the extent that these functions must be regulated to ensure maintenance. In the bone marrow, some HSCs localize at or near the endosteum (the interface of bone and bone marrow), whereas other HSCs localize around sinusoidal blood vessels, and in other locations. It is not clear whether there are multiple Niches in these locations, or whether HSCs only transiently migrate through some of these locations. Osteoblasts and osteoclasts at the endosteum have been proposed to form a niche for HSCs in the bone marrow, though it remains uncertain whether this niche is at the endosteal surface or whether these cells secrete factors that influence Niches located close to, but not at, the endosteal surface. As HSCs expand during fetal development, and engage in adult extramedullary haematopoiesis in tissues such as the liver and spleen that contain no bone or endosteum, endosteal cells cannot be the only cell types capable of creating HSC Niches. The presence of HSCs around sinusoids in bone marrow and extramedullary tissues raises the possibility that at least some HSCs reside in perivascular Niches. Some perivascular cells also appear to secrete factors implicated in HSC maintenance, though additional work will be required to determine whether this constitutes a bona fide niche. One possibility is that endosteal cells and perivascular cells work together to create a common niche near the endosteum in the trabecular zone of bone. It is also possible that there are multiple different Niches in haematopoietic tissues that perform redundant or distinct roles in the maintenance of HSCs and the regulation of haematopoiesis. Many of the mechanisms by which proposed Niches have been suggested to promote HSC maintenance would benefit from additional studies to determine whether such mechanisms are required for HSC maintenance in vivo or to confirm through conditional deletion which cells are most responsible for the expression of key factors.
Colette M St Mary - One of the best experts on this subject based on the ideXlab platform.
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The evolutionary trade‐off between stem cell niche size, aging, and tumorigenesis
Evolutionary Applications, 2017Co-Authors: Vincent L. Cannataro, Scott A. Mckinley, Colette M St MaryAbstract:Many epithelial tissues within multicellular organisms are continually replenished by small independent populations of stem cells largely responsible for maintaining tissue homeostasis. These continually dividing populations are subject to mutations that can lead to tumorigenesis but also contribute to aging. Mutations accumulate in stem cell Niches and change the rate of cell division and differentiation; the pace of this process and the fate of specific mutations depend strongly on niche population size. Here, we create a mathematical model of the intestinal stem cell niche, crypt system, and epithelium. We calculate the expected effect of fixed mutations in stem cell Niches and their effect on tissue homeostasis throughout the intestinal epithelium over organismal lifetime. We find that, due to the small population size of stem cell Niches, mutations predominantly fix via genetic drift and decrease stem cell fitness, leading to niche and tissue attrition, and contributing to organismal aging. We also explore mutation accumulation at various stem cell niche sizes and demonstrate that an evolutionary trade-off exists between niche size, tissue aging, and the risk of tumorigenesis. Further, mouse and human Niches exist at a size that minimizes the probability of tumorigenesis, at the expense of accumulating deleterious mutations due to genetic drift. Finally, we show that the trade-off between the probability of tumorigenesis and the extent of aging depends on whether or not mutational effects confer a selective advantage in the stem cell niche.
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The Evolutionary Trade-off between Stem Cell Niche Size, Aging, and Tumorigenesis
bioRxiv, 2016Co-Authors: Vincent L. Cannataro, Scott A. Mckinley, Colette M St MaryAbstract:Many epithelial tissues within large multicellular organisms are continually replenished by small independent populations of stem cells. These stem cells divide within their Niches and differentiate into the constituent cell types of the tissue, and are largely responsible for maintaining tissue homeostasis. Mutations can accumulate in stem cell Niches and change the rate of stem cell division and differentiation, contributing to both aging and tumorigenesis. Here, we create a mathematical model of the intestinal stem cell niche, crypt system, and epithelium. We calculate the expected effect of fixed mutations in stem cell Niches and their expected effect on tissue homeostasis throughout the intestinal epithelium over the lifetime of an organism. We find that, due to the small population size of stem cell Niches, fixed mutations are expected to accumulate via genetic drift and decrease stem cell fitness, leading to niche and tissue attrition, and contributing to organismal aging. We also explore mutation accumulation at various stem cell niche sizes, and demonstrate that an evolutionary trade-off exists between niche size, tissue aging, and the risk of tumorigenesis; where Niches exist at a size that minimizes the probability of tumorigenesis, at the expense of accumulating deleterious mutations due to genetic drift. Finally, we show that the probability of tumorigenesis and the extent of aging trade-off differently depending on whether mutational effects confer a selective advantage, or not, in the stem cell niche.
Vincent L. Cannataro - One of the best experts on this subject based on the ideXlab platform.
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The evolutionary trade‐off between stem cell niche size, aging, and tumorigenesis
Evolutionary Applications, 2017Co-Authors: Vincent L. Cannataro, Scott A. Mckinley, Colette M St MaryAbstract:Many epithelial tissues within multicellular organisms are continually replenished by small independent populations of stem cells largely responsible for maintaining tissue homeostasis. These continually dividing populations are subject to mutations that can lead to tumorigenesis but also contribute to aging. Mutations accumulate in stem cell Niches and change the rate of cell division and differentiation; the pace of this process and the fate of specific mutations depend strongly on niche population size. Here, we create a mathematical model of the intestinal stem cell niche, crypt system, and epithelium. We calculate the expected effect of fixed mutations in stem cell Niches and their effect on tissue homeostasis throughout the intestinal epithelium over organismal lifetime. We find that, due to the small population size of stem cell Niches, mutations predominantly fix via genetic drift and decrease stem cell fitness, leading to niche and tissue attrition, and contributing to organismal aging. We also explore mutation accumulation at various stem cell niche sizes and demonstrate that an evolutionary trade-off exists between niche size, tissue aging, and the risk of tumorigenesis. Further, mouse and human Niches exist at a size that minimizes the probability of tumorigenesis, at the expense of accumulating deleterious mutations due to genetic drift. Finally, we show that the trade-off between the probability of tumorigenesis and the extent of aging depends on whether or not mutational effects confer a selective advantage in the stem cell niche.
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The Evolutionary Trade-off between Stem Cell Niche Size, Aging, and Tumorigenesis
bioRxiv, 2016Co-Authors: Vincent L. Cannataro, Scott A. Mckinley, Colette M St MaryAbstract:Many epithelial tissues within large multicellular organisms are continually replenished by small independent populations of stem cells. These stem cells divide within their Niches and differentiate into the constituent cell types of the tissue, and are largely responsible for maintaining tissue homeostasis. Mutations can accumulate in stem cell Niches and change the rate of stem cell division and differentiation, contributing to both aging and tumorigenesis. Here, we create a mathematical model of the intestinal stem cell niche, crypt system, and epithelium. We calculate the expected effect of fixed mutations in stem cell Niches and their expected effect on tissue homeostasis throughout the intestinal epithelium over the lifetime of an organism. We find that, due to the small population size of stem cell Niches, fixed mutations are expected to accumulate via genetic drift and decrease stem cell fitness, leading to niche and tissue attrition, and contributing to organismal aging. We also explore mutation accumulation at various stem cell niche sizes, and demonstrate that an evolutionary trade-off exists between niche size, tissue aging, and the risk of tumorigenesis; where Niches exist at a size that minimizes the probability of tumorigenesis, at the expense of accumulating deleterious mutations due to genetic drift. Finally, we show that the probability of tumorigenesis and the extent of aging trade-off differently depending on whether mutational effects confer a selective advantage, or not, in the stem cell niche.
Allan C Spradling - One of the best experts on this subject based on the ideXlab platform.
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the drosophila ovarian and testis stem cell Niches similar somatic stem cells and signals
Developmental Cell, 2005Co-Authors: Eva Decotto, Allan C SpradlingAbstract:Summary The stem cell Niches at the apex of Drosophila ovaries and testes have been viewed as distinct in two major respects. While both contain germline stem cells, the testis niche also contains "cyst progenitor" stem cells, which divide to produce somatic cells that encase developing germ cells. Moreover, while both Niches utilize BMP signaling, the testis niche requires a key JAK/STAT signal. We now show, by lineage marking, that the ovarian niche also contains a second type of stem cell. These "escort stem cells" morphologically resemble testis cyst progenitor cells and their daughters encase developing cysts before undergoing apoptosis at the time of follicle formation. In addition, we show that JAK/STAT signaling also plays a critical role in ovarian niche function, and acts within escort cells. These observations reveal striking similarities in the stem cell Niches of male and female gonads, and suggest that they are largely governed by common mechanisms.
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an empty drosophila stem cell niche reactivates the proliferation of ectopic cells
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Toshie Kai, Allan C SpradlingAbstract:Stem cells are thought to reside in regulatory microenvironments (“Niches”) generated by stable stromal neighbors. To investigate the significance of empty Niches vacated by stem cell loss, we studied Drosophila ovarioles, which maintain two to three germ-line stem cells in a niche requiring adhesive stromal cap cells and Decapentaplegic signals. After experimentally emptying the germ-line stem cell niche, cap cell activity persists for several weeks. Initially, somatic inner germarium sheath cells enter the empty niche, respond to Dpp, but fail to divide. Subsequently, follicle cell progenitors, including somatic stem cells enter the niche, respond to Dpp, and proliferate as long as cap cells remain. Proliferation requires the normal hedgehog signal of the somatic stem cells as well as proximity to the niche. Thus, empty Niches can persist, signal incoming cells, and support ectopic proliferation. Similar events may underlie some disease states.
Genevieve M Crane - One of the best experts on this subject based on the ideXlab platform.
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Adult haematopoietic stem cell Niches
Nature Reviews Immunology, 2017Co-Authors: Genevieve M Crane, Elise Jeffery, Sean J MorrisonAbstract:Recent advances in imaging techniques and genetic tools have rapidly increased our understanding of the Niches that maintain adult haematopoietic stem cells, including the constituent cell types and the factors that directly or indirectly regulate these Niches. Dividing and non-dividing haematopoietic stem cells (HSCs) reside in perivascular Niches that are mainly associated with sinusoidal blood vessels in adult bone marrow and spleen. A subset of HSCs is most closely associated with arterioles. The periarteriolar and perisinusoidal microenvironments differ in terms of the capacity of HSCs to intravasate into the circulation and in terms of their exposure to blood plasma components. Endothelial cells and leptin receptor-expressing, CXC-chemokine ligand 12 (CXCL12)-abundant reticular perivascular stromal cells are the main sources of the stem cell factor (SCF) and CXCL12 required for HSC maintenance in normal young-adult bone marrow. Other perivascular cells, such as Ng2 -CreER^+ periarteriolar cells (which express neural–glial antigen 2), may or may not also synthesize the CXCL12 required for HSC maintenance. Several other cell types — including megakaryocytes, monocytes and macrophages, neurons (specifically, nerve fibres) and Schwann cells — directly or indirectly regulate HSC or niche function through other mechanisms. Extramedullary haematopoiesis in the spleen depends on a perivascular niche that is associated with sinusoids in the red pulp, in which endothelial cells and transcription factor 21-expressing stromal cells are the main sources of SCF and CXCL12. This niche is necessary for the recovery of haematopoiesis from haematopoietic stresses such as blood loss. The vascular and stromal compositions of the bone marrow change during ageing. Stem cell Niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the Niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo , and improved imaging techniques. Together, they have shown that HSC Niches are perivascular in the bone marrow and spleen. Endothelial cells and mesenchymal stromal cells secrete factors that promote HSC maintenance in these Niches, but other cell types also directly or indirectly regulate HSC Niches.
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adult haematopoietic stem cell Niches
Nature Reviews Immunology, 2017Co-Authors: Genevieve M Crane, Elise Jeffery, Sean J MorrisonAbstract:Stem cell Niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the Niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. Together, they have shown that HSC Niches are perivascular in the bone marrow and spleen. Endothelial cells and mesenchymal stromal cells secrete factors that promote HSC maintenance in these Niches, but other cell types also directly or indirectly regulate HSC Niches.
