Your browser doesn't support javascript.
loading
Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program.
Gao, Longfei; Lee, Heather; Goodman, Joshua H; Ding, Lei.
Afiliação
  • Gao L; Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Lee H; Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Goodman JH; Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Ding L; Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: ld2567@cumc.columbia.edu.
Cell ; 187(11): 2801-2816.e17, 2024 May 23.
Article em En | MEDLINE | ID: mdl-38657601
ABSTRACT
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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Nicho de Células-Tronco / Células-Tronco Mesenquimais / Metiltransferases / Camundongos Endogâmicos C57BL Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Nicho de Células-Tronco / Células-Tronco Mesenquimais / Metiltransferases / Camundongos Endogâmicos C57BL Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos