生物
干细胞
间充质干细胞
利基
细胞生物学
造血
造血干细胞
骨髓
干细胞巢
免疫学
祖细胞
生物化学
作者
Longfei Gao,Heather Lee,Joshua Goodman,Lei Ding
出处
期刊:Cell
[Elsevier]
日期:2024-04-01
被引量:1
标识
DOI:10.1016/j.cell.2024.03.032
摘要
Summary
The niche is typically considered as a pre-established structure sustaining stem cells. Therefore, the regulation of its formation remains largely unexplored. Whether distinct molecular mechanisms control the establishment versus maintenance of a stem cell niche is unknown. To address this, we compared perinatal and adult bone marrow mesenchymal stromal cells (MSCs), a key component of the hematopoietic stem cell (HSC) niche. MSCs exhibited enrichment in genes mediating m6A mRNA methylation at the perinatal stage and downregulated the expression of Mettl3, the m6A methyltransferase, shortly after birth. Deletion of Mettl3 from developing MSCs but not osteoblasts led to excessive osteogenic differentiation and a severe HSC niche formation defect, which was significantly rescued by deletion of Klf2, an m6A target. In contrast, deletion of Mettl3 from MSCs postnatally did not affect HSC niche. Stem cell niche generation and maintenance thus depend on divergent molecular mechanisms, which may be exploited for regenerative medicine.
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