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2017 ; 8
(1
): 541
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A CRISPR screen identifies genes controlling Etv2 threshold expression in murine
hemangiogenic fate commitment
#MMPMID28912455
Zhao H
; Choi K
Nat Commun
2017[Sep]; 8
(1
): 541
PMID28912455
show ga
The ETS transcription factor Etv2 is necessary and sufficient for the generation
of hematopoietic and endothelial cells. However, upstream regulators of Etv2 in
hemangiogenesis, generation of hematopoietic and endothelial cells, have not been
clearly addressed. Here we track the developmental route of hemangiogenic
progenitors from mouse embryonic stem cells, perform genome-wide CRISPR
screening, and transcriptome analysis of en route cell populations by utilizing
Brachyury, Etv2, or Scl reporter embryonic stem cell lines to further understand
the mechanisms that control hemangiogenesis. We identify the forkhead
transcription factor Foxh1, in part through Eomes, to be critical for the
formation of FLK1(+) mesoderm, from which the hemangiogenic fate is specified.
Importantly, hemangiogenic fate is specified not simply by the onset of Etv2
expression, but by a threshold-dependent mechanism, in which VEGF-FLK1 signaling
plays an instructive role by promoting Etv2 threshold expression. These studies
reveal comprehensive cellular and molecular pathways governing the hemangiogenic
cell lineage development.How haematopoietic and endothelial cell lineages are
specified is unclear. Here, the authors identify the forkhead transcription
factor Foxh1 as regulating FLK1+ mesoderm formation in mouse embryonic stem
cells, which in turn specifies hemangiogenic fate via Etv2.
|*Cell Differentiation
[MESH]
|*Clustered Regularly Interspaced Short Palindromic Repeats
[MESH]