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Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors.

Abstract：

:Hematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin(-)Sca-1(+)c-Kit(+)) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein α (C/EBPα) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPα, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP(+) cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPα induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP(+) cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP(+) multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPα in multipotent hematopoietic and thymic progenitors.

journal_name

Blood

journal_title

Blood

authors

Wölfler A,Danen-van Oorschot AA,Haanstra JR,Valkhof M,Bodner C,Vroegindeweij E,van Strien P,Novak A,Cupedo T,Touw IP

doi

10.1182/blood-2010-03-275404

subject

Has Abstract

pub_date

2010-11-18 00:00:00

pages

4116-25

issue

20

eissn

0006-4971

issn

1528-0020

pii

blood-2010-03-275404

journal_volume

116

pub_type

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