p21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells.
Protein Cell
; 2024 May 09.
Article
in En
| MEDLINE
| ID: mdl-38721703
ABSTRACT
The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Protein Cell
Journal subject:
BIOQUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Alemania