| RRC ID |
87954
|
| Author |
Lizama CO, Hawkins JS, Schmitt CE, Bos FL, Zape JP, Cautivo KM, Borges Pinto H, Rhyner AM, Yu H, Donohoe ME, Wythe JD, Zovein AC.
|
| Title |
Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition.
|
| Journal |
Nat Commun
|
| Abstract |
Changes in cell fate and identity are essential for endothelial-to-haematopoietic transition (EHT), an embryonic process that generates the first adult populations of haematopoietic stem cells (HSCs) from hemogenic endothelial cells. Dissecting EHT regulation is a critical step towards the production of in vitro derived HSCs. Yet, we do not know how distinct endothelial and haematopoietic fates are parsed during the transition. Here we show that genes required for arterial identity function later to repress haematopoietic fate. Tissue-specific, temporally controlled, genetic loss of arterial genes (Sox17 and Notch1) during EHT results in increased production of haematopoietic cells due to loss of Sox17-mediated repression of haematopoietic transcription factors (Runx1 and Gata2). However, the increase in EHT can be abrogated by increased Notch signalling. These findings demonstrate that the endothelial haematopoietic fate switch is actively repressed in a population of endothelial cells, and that derepression of these programs augments haematopoietic output.
|
| Volume |
6
|
| Pages |
7739
|
| Published |
2015-7-23
|
| DOI |
10.1038/ncomms8739
|
| PII |
ncomms8739
|
| PMID |
26204127
|
| PMC |
PMC4519987
|
| MeSH |
Animals
Blood Vessels / embryology*
Core Binding Factor Alpha 2 Subunit / metabolism*
Female
GATA2 Transcription Factor / metabolism*
Genes, Reporter
HMGB Proteins / physiology*
Hemangioblasts / physiology*
Hematopoiesis
Mice
Pregnancy
Receptor, Notch1 / metabolism
SOXF Transcription Factors / physiology*
|
| IF |
12.121
|
| Resource |
| Mice |
RBRC06137 |
