Musashi-2 controls cell fate, lineage bias, and TGF-ß signaling in HSCs.
J Exp Med
; 211(1): 71-87, 2014 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-24395885
ABSTRACT
Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-ß signaling. Msi2-null HSCs are insensitive to TGF-ß-mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Transdução de Sinais
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Divisão Celular
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Proteínas de Ligação a RNA
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Hematopoese
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2014
Tipo de documento:
Article