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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

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

ORGANISM(S): Mus musculus

PROVIDER: GSE217057 | GEO | 2024/04/23

REPOSITORIES: GEO

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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

Project description:The niche is typically considered as a pre-established structure sustaining stem cells. Therefore, the regulation of its formation remains largely unexplored. It is unknown whether distinct molecular mechanisms control the establishment versus maintenance of a stem cell niche. To address this, we compared perinatal with adult bone marrow mesenchymal stromal cells (MSCs), a key component of the hematopoietic stem cell (HSC) niche. MSCs exhibited an enrichment in genes mediating m6A mRNA methylation regulation at the perinatal stage and downregulated the expression of Mettl3, the m6A methyltransferase, shortly after birth. Deletion of Mettl3 from developing MSCs led to excessive osteogenic differentiation and a severe HSC niche formation defect, which was rescued by deletion of Klf2, a target of m6A. In contrast, deletion of Mettl3 from MSCs postnatally did not affect HSC niche or hematopoiesis. Stem cell niche generation and maintenance thus depend on divergent molecular mechanisms, which may be exploited for regenerative medicine.

2024-04-23 | GSE217055 | GEO

Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program

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Hematopoietic stem cell niche maintenance during homeostasis and regeneration.

Project description:The bone marrow niche has mystified scientists for many years, leading to widespread investigation to shed light into its molecular and cellular composition. Considerable efforts have been devoted toward uncovering the regulatory mechanisms of hematopoietic stem cell (HSC) niche maintenance. Recent advances in imaging and genetic manipulation of mouse models have allowed the identification of distinct vascular niches that have been shown to orchestrate the balance between quiescence, proliferation and regeneration of the bone marrow after injury. Here we highlight the recently discovered intrinsic mechanisms, microenvironmental interactions and communication with surrounding cells involved in HSC regulation, during homeostasis and in regeneration after injury and discuss their implications for regenerative therapy.

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

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The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche.

Project description:The balance between survival and death in many cell types is regulated by small changes in the intracellular content of bioactive sphingolipids. Enzymes that either produce or degrade these sphingolipids control this equilibrium. The findings here described indicate that the lysosomal galactocerebrosidase (GALC) enzyme, defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell (HSPC) niche by contributing to the control of the intracellular content of key sphingolipids. Indeed, we show that both insufficient and supraphysiologic GALC activity-by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model-induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect HSPC survival and function and the functionality of the stem cell niche. Therefore, GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Molecular analysis of the subaortic hematopoietic stem cell niche

Project description:This SuperSeries is composed of the SubSeries listed below.

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