C/EBPß isoforms sequentially regulate regenerating mouse hematopoietic stem/progenitor cells.
Blood Adv
; 4(14): 3343-3356, 2020 07 28.
Article
en En
| MEDLINE
| ID: mdl-32717031
ABSTRACT
The transcription factor CCAAT enhancer-binding protein ß (C/EBPß) is required for stress-induced granulopoiesis at the level of hematopoietic stem/progenitor cells (HSPCs); however, its role and mechanisms of action in HSPCs are unknown. In this study, we assessed the regulation and functions of C/EBPß in HSPCs, especially under stress conditions. After 5-fluorouracil treatment or bone marrow transplantation, Cebpb-/- HSPCs exhibited impaired cell-cycle activation and myeloid differentiation at the early and late phases of regeneration, respectively, whereas at steady state, Cebpb deficiency did not affect HSPCs. C/EBPß was upregulated in response to hematopoietic stress, especially in CD150high long term-hematopoietic stem cells (LT-HSCs). Intracellular flow cytometric analysis that detected distinct domains of C/EBPß revealed that, among the 3 isoforms of C/EBPß, liver-enriched inhibitory protein (LIP) was upregulated in LT-HSCs prior to liver-enriched activating protein (LAP)/LAP* during regeneration. Early upregulation of LIP promoted cell-cycle entry of LT-HSCs by positively regulating Myc and expanded the HSPCs pool. Subsequent myeloid differentiation of amplified HSPCs was mediated by LAP/LAP*, which were upregulated at a later phase of regeneration. Collectively, our findings show that stress-induced sequential upregulation of C/EBPß isoforms is critical for fine-tuning the proliferation and differentiation of regenerating HSPCs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Trasplante de Células Madre Hematopoyéticas
Límite:
Animals
Idioma:
En
Revista:
Blood Adv
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón