Transcriptomics

Dataset Information

42

Chd1 is essential in the endothelial lineage for the emergence of definitive hematopoietic stem/progenitor cells


ABSTRACT: Lineage specification during development involves reprogramming of chromatin states, but little is known about how this is regulated in vivo. We previously showed that the chromatin remodeler Chd1 regulates transcriptional output and self-renewal of mouse embryonic stem cells, and is essential for epiblast development. These results raise the question of whether Chd1 regulates the development of other progenitor populations. Here we report that endothelial-specific deletion of Chd1 using Tie2-Cre leads to embryonic lethality by E15.5. Development of the vasculature and of primitive hematopoiesis appears to occur normally in the mutants. However, mutant embryos show signs of anemia as early as E11.5, are depleted of definitive hematopoietic stem /progenitor cells, and display a complete failure of fetal liver erythropoiesis. While mutants at E10.5 appear morphologically normal and can develop hemogenic clusters in the dorsal aorta, the E10.5 mutant endothelium fails to activate a transcriptional program associated with hematopoiesis. This transcriptional program may serve as a resource for the identification of novel markers or regulators of definitive hematopoiesis. Finally, hematopoietic-specific Chd1 deletion using Vav-Cre yields no apparent defects during development or adulthood. These results suggest that Chd1 regulates chromatin-remodeling events critical for a specific developmental window during the transition of endothelial cells to definitive blood progenitors. Analysis of CD31+ tdTomato+ cells sorted from E10.5 whole embryos with an endothelial-specific deletion of Chd1, using 4 biological replicates of 2 genotypes (CreHet controls vs mutants).

ORGANISM(S): Mus musculus  

SUBMITTER: Fong Ming Koh  Carlos O Lizama   Miguel Ramalho-Santos   Priscilla Wong   John S Hawkins   Ann C Zovein   Fong M Koh    

PROVIDER: E-GEOD-62796 | ArrayExpress | 2015-03-07

SECONDARY ACCESSION(S): GSE62796PRJNA265163

REPOSITORIES: GEO, ArrayExpress

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