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Ceramide blockade in murine hematopoietic stem cells

ABSTRACT: Ceramide blockade in murine hematopoietic stem cells

PROVIDER: PRJNA939906 | ENA |

REPOSITORIES: ENA

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Ceramide blockade in murine hematopoietic stem cells

Project description:Hematopoietic stem and progenitor cells (HSPCs) rely upon cellular crosstalk, including extracellular vesicles (EVs) for lifelong niche occupancy and cellular function. Vesicle secretion is tightly linked to intracellular homeostasis; however, these mechanisms are poorly understood in HSPCs, particularly at the single-cell level. In this study, we target ceramide-dependent EV secretion by pharmacologic blockade in ex vivo expanded HSPCs. We use these cells to investigate single-cell resolution of short-term and delayed transcriptional changes induced by ceramide-EV inhibition.

2023-10-01 | GSE226348 | GEO

Ceramide-dependent vesicle secretion modulates the integrated stress response in hematopoietic stem cells

Project description:Cellular crosstalk within the bone marrow niche maintains hematopoietic stem and progenitor cell (HSPC) integrity and safeguards lifelong blood and immune cell production. Deeper understanding of reciprocal niche signals governing crucial properties of HSPCs is relevant to the pathophysiology of blood disorders and improving HSPC transplantation. Extracellular vesicles (EVs) are key factors of the HSPC secretome, providing signals that regulate homeostasis and stemness. Here we demonstrate ex vivo blockade of ceramide-dependent vesicle secretion from HSPCs activates an integrated stress response (ISR), promoting downstream mTOR inhibition and metabolic quiescence. Crucially, ceramide-EV depletion leads to striking improvements in long-term transplantation. The aggregate findings link ceramide-dependent EV secretion and the ISR as a regulatory dyad guarding HSPC homeostasis and long-term fitness. Translationally, these data support exploration of ceramide inhibition during ex vivo maintenance of HSPCs for adoptive transfer.

2024-11-12 | PXD040865 | Pride

Expression data from murine hematopoietic stem cells

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Hematopoietic stem cells (HSCs)

Project description:G0 marker-separation of dormant and active hematopoietic stem cells reveals dormancy regulation by basal cytoplasmic calcium

2019-12-19 | PXD012093 | JPOST Repository

GATA2 mutant transduction of murine hematopoietic stem cells

Project description:GATA2 mutant transduction of murine hematopoietic stem cells

2018-09-01 | GSE111328 | GEO

GATA2 mutant transduction of murine hematopoietic stem cells

Project description:GATA2 mutant transduction of murine hematopoietic stem cells

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Expression data from murine hematopoietic stem cells

Project description:Long-term hematopoietic output is dependent on the hematopoietic stem cell (HSC) homeostasis which is maintained by a complex network of molecules. Among these, microRNAs (miRNAs) play crucial roles, while the underlying molecular basis have not been fully demonstrated. Here, we found that miR-21 is enriched in murine HSCs. Then, we generated a polyinosinic:polycytidylic acid (pIpC)-inducible mouse model (miR-21flox/flox:Mx1-Cre) to obtain a specific deletion of miR-21 in hematopoietic system. It was found that mice with conditional knockout of miR-21 exhibit an obvious perturbation of normal hematopoiesis.Further researches reveal that miR-21 deficiency affect HSC homeostasis and function. We used microarrays to detail the global programme of gene expression, and identified distinct classes of up-regulated and down-regulated genes in murine HSCs after miR-21 conditional knockout.

2021-02-08 | GSE131603 | GEO

Mettl3-dependent m6A targets in adult murine hematopoietic stem cells

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A comprehensive transcriptome signature of murine hematopoietic stem cell aging

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miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

2017-01-11 | PXD003931 | Pride

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