Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium.
Development
; 145(5)2018 03 12.
Article
em En
| MEDLINE
| ID: mdl-29530939
ABSTRACT
During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation. The use of inducible Runx1 expression combined with alterations in the expression of the RUNX1 co-factor CBFß allowed us to evaluate a wide range of RUNX1 levels. We demonstrate that low RUNX1 levels are sufficient and necessary to initiate an effective endothelial-to-hematopoietic transition. Subsequently, RUNX1 is also required to complete the endothelial-to-hematopoietic transition and to generate functional hematopoietic precursors. In contrast, elevated levels of RUNX1 are able to drive an accelerated endothelial-to-hematopoietic transition, but the resulting cells are unable to generate mature hematopoietic cells. Together, our results suggest that RUNX1 dosage plays a pivotal role in hemogenic endothelium maturation and the establishment of the hematopoietic system.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Endotélio Vascular
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Dosagem de Genes
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Subunidade alfa 2 de Fator de Ligação ao Core
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Hemangioblastos
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Hematopoese
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article