KBTBD4-mediated reduction of MYC is critical for hematopoietic stem cell expansion upon UM171 treatment.
Blood
; 143(10): 882-894, 2024 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-38207291
ABSTRACT
ABSTRACT Ex vivo expansion of hematopoietic stem cells (HSCs) is gaining importance for cell and gene therapy, and requires a shift from dormancy state to activation and cycling. However, abnormal or excessive HSC activation results in reduced self-renewal ability and increased propensity for myeloid-biased differentiation. We now report that activation of the E3 ligase complex CRL3KBTBD4 by UM171 not only induces epigenetic changes through CoREST1 degradation but also controls chromatin-bound master regulator of cell cycle entry and proliferative metabolism (MYC) levels to prevent excessive activation and maintain lympho-myeloid potential of expanded populations. Furthermore, reconstitution activity and multipotency of UM171-treated HSCs are specifically compromised when MYC levels are experimentally increased despite degradation of CoREST1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Transplante de Células-Tronco Hematopoéticas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article