Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition

Carlos O. Lizama, John S. Hawkins, Christopher E. Schmitt, Frank L. Bos, Joan P. Zape, Kelly M. Cautivo, Hugo Borges Pinto, Alexander M. Rhyner, Hui Yu, Mary E. Donohoe, Joshua D. Wythe and Ann C. Zovein ()
Additional contact information
Carlos O. Lizama: Cardiovascular Research Institute, University of California, San Francisco
John S. Hawkins: Cardiovascular Research Institute, University of California, San Francisco
Christopher E. Schmitt: Cardiovascular Research Institute, University of California, San Francisco
Frank L. Bos: Cardiovascular Research Institute, University of California, San Francisco
Joan P. Zape: Cardiovascular Research Institute, University of California, San Francisco
Kelly M. Cautivo: Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile
Hugo Borges Pinto: Burke Medical Research Institute
Alexander M. Rhyner: Baylor College of Medicine
Hui Yu: Cardiovascular Research Institute, University of California, San Francisco
Mary E. Donohoe: Burke Medical Research Institute
Joshua D. Wythe: Baylor College of Medicine
Ann C. Zovein: Cardiovascular Research Institute, University of California, San Francisco

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8739 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8739

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8739

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().