@article{ab1b74cd136b4911853767a8d46ad746,
title = "Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition",
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.",
author = "Lizama, {Carlos O.} and Hawkins, {John S.} and Schmitt, {Christopher E.} and Bos, {Frank L.} and Zape, {Joan P.} and Cautivo, {Kelly M.} and {Borges Pinto}, Hugo and Rhyner, {Alexander M.} and Hui Yu and Donohoe, {Mary E.} and Wythe, {Joshua D.} and Zovein, {Ann C.}",
note = "Funding Information: We thank Juan Carlos Z{\'u}{\~n}iga-Pfl{\"u}cker PhD of Sunnybrook Health Sciences Centre in Toronto for the OP9-Dl1 cell lines, Yomiko Saga PhD of National Genetics Institutes of Japan and RIKEN BRC for use of the TP1-Venus (ICR) mouse line, Courtney Griffin PhD of the University of Oklahoma Health Sciences Center for the C166 cell line and advisement on luciferase protocols, and Mary Dickinson of the Baylor College of Medicine for the Mlc2a mutant mouse line. We also thank Joanna Tober PhD of the Speck lab in the University of Pennsylvania for her help and advice on methycellulose colony excision genotyping and Ralph Adams PhD of Max Planck Institute for use of his Cdh5(PAC)-CreERT2 line. This work was supported by the American Heart Association Scientist Development Grant (J.D.W.), Burroughs Wellcome Fund Career Award for Medical Scientists (A.C.Z.) and the NIH Office of the Director{\textquoteright}s Innovator Award program (A.C.Z.). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = jul,
day = "23",
doi = "10.1038/ncomms8739",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}