| First Author | Gao L | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 11 | Pages | 2801-2816.e17 |
| PubMed ID | 38657601 | Mgi Jnum | J:348312 |
| Mgi Id | MGI:7641193 | Doi | 10.1016/j.cell.2024.03.032 |
| Citation | Gao L, et al. (2024) Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program. Cell |
| abstractText | 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 m(6)A mRNA methylation at the perinatal stage and downregulated the expression of Mettl3, the m(6)A 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 m(6)A 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. |
