Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition
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 productio...
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Published in | Nature communications Vol. 6; no. 1; p. 7739 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
23.07.2015
Nature Publishing Group Nature Pub. Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
The first haematopoietic stem and progenitor cells arise from the hemogenic endothelium of arterial vascular beds. Here the authors describe the mechanism that regulates the endothelial-to-haematopoietic transition and show that
Sox17
and
Notch1
, genes critical to arterial endothelium identity, are also crucial repressors of haematopoietic fate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms8739 |