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

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

PROVIDER: PRJNA718093 | ENA |

REPOSITORIES: ENA

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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.

| PRJNA718089 | ENA

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.

2021-03-29 | GSE171014 | GEO

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]

| PRJNA718091 | ENA

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

2021-03-29 | GSE171013 | GEO

Stem cell competition orchestrates skin homeostasis and ageing

Project description:Stem cell competition orchestrates skin homeostasis and ageing

| PRJNA438288 | ENA

Stem cell competition orchestrates skin homeostasis and ageing

Project description:Stem cells underlie tissue homeostasis, but their dynamics during ageing—and the relevance of these dynamics to organ ageing—remain unknown. Here we report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modelling show that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing. Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention.

2019-04-05 | GSE111825 | GEO

Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche

Project description:In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically-defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells toward FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on “mitogen competition”. We propose that this model provides a generic and robust mechanism to support stem cell homeostasis in open, or facultative, niche environments.

2018-12-19 | GSE118846 | GEO

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. Using genetic mosaic mouse models and bone marrow chimeras, we have characterized 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. This microarray experiment is aimed at identification of candidate genes that mediate this competition. It compares mRNA expression patterns of HSCs with different levels of p53 activity in either competitive or non-competitive conditions (isolated from either wild type, mutant p53, or mosaic wt/mutant p53 mice (R26-mp53mice) after irradiation).

2010-04-01 | GSE20912 | GEO

The CKS1/CKS2 proteostasis axis is crucial to maintain hematopoietic stem cell function

Project description:Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification and degradation – broadly termed protein homeostasis or “proteostasis” – in these cells is still in its infancy. Here we report the requirement of the small phospho-binding adaptor proteins, the cyclin dependent kinase subunits (Cks1 and Cks2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. Cks1 and Cks2 are critical regulators of a myriad of key intracellular signalling pathways that govern hematopoietic stem cell biology and together they balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function.

2023-03-11 | PXD035984 | Pride

Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche

Project description:Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche

| PRJNA486990 | ENA