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Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE171015 | GEO | 2021/03/29

REPOSITORIES: GEO

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Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [scRNA-seq]

Project description:Cellular competition for limiting hematopoietic factors is a physiologically regulated but poorly understood process. Here, we studied this phenomenon by hampering hematopoietic progenitor access to Leptin receptor+ mesenchymal stem/progenitor cells (MSPCs) and endothelial cells (ECs). We showed that HSC numbers increased by 2-fold when multipotent and lineage-restricted progenitors fail to respond to CXCL12 produced by MSPCs and ECs. HSCs were qualitatively normal, and HSC expansion only occurred when early hematopoietic progenitors but not differentiated hematopoietic cells lacked CXCR4. Furthermore, the MSPC and EC transcriptomic heterogeneity was remarkably stable, suggesting that it is impervious to dramatic changes in hematopoietic progenitor interactions. Instead, HSC expansion was caused by increased availability of membrane-bound stem cell factor (mSCF) on MSPCs and ECs due to reduced consumption by cKit-expressing hematopoietic progenitors. These studies revealed an intricate homeostatic balance between HSCs and proximal hematopoietic progenitors regulated by cell competition for limiting amounts of mSCF.

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Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [bulk RNA-seq]

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Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis.

Project description:Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis.

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p53-mediated hematopoietic stem and progenitor cell competition.

Project description:Cell competition was originally described in Drosophila as a process for selection of the fittest cells. It is likely to play an important role in tissue homeostasis in all metazoans, but little is known about its role and regulation in mammals. By using genetic mosaic mouse models and bone marrow chimeras, we describe here a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell-autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells.

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Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [bulk RNA-seq]

Project description:Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [bulk RNA-seq]

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Functional Niche Competition Between Normal Hematopoietic Stem and Progenitor Cells and Myeloid Leukemia Cells.

Project description:Hematopoietic stem and progenitor cells (HSPCs) reside in a specialized niche that regulates their proliferative capacity and their fate. There is increasing evidence for similar roles of marrow niches on controlling the behavior of leukemic cells; however, whether normal hematopoietic stem cell (HSC) and leukemic cells reside in or functionally compete for the same marrow niche is unclear. We used the mixed lineage leukemia-AF9 (MLL-AF9) murine acute myeloid leukemia (AML) in a competitive repopulation model to investigate whether normal HSPC and leukemic cells functionally compete for the same marrow niches. Irradiated recipient mice were transplanted with fixed numbers of MLL-AF9 cells mixed with increasing doses of normal syngeneic whole bone marrow (WBM) or with purified HSPC (LSK). Survival was significantly increased and leukemic progression was delayed proportional to increasing doses of normal WBM or normal LSK cells in multiple independent experiments, with all doses of WBM or LSK cells studied above the threshold for rapid and complete hematopoietic reconstitution in the absence of leukemia. Confocal microscopy demonstrated nests of either leukemic cells or normal hematopoietic cells but not both in the marrow adjacent to endosteum. Early following transplantation, leukemic cells from animals receiving lower LSK doses were cycling more actively than in those receiving higher doses. These results suggest that normal HSPC and AML cells compete for the same functional niche. Manipulation of the niche could impact on response to antileukemic therapies, and the numbers of normal HSPC could impact on leukemia outcome, informing approaches to cell dose in the context of stem cell transplantation.

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Histone Demethylase Lsd1 Represses Hematopoietic Stem and Progenitor Cell Signatures During Blood Cell Maturation.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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