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

GSE217055 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/04/23 Platform GPL19057
Summary
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.
Published in
Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program
Gao L, Lee H, Goodman JH et al. · Cell 2024 · PMID 38657601 · doi:10.1016/j.cell.2024.03.032
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Also filed as BioProject PRJNA896638 and SRA study SRP405727. Searching any of these in the dataset finder brings you back here.

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