Journal article
Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
- Abstract:
-
Haematopoietic stem cells are generated from the haemogenic endothelium (HE) located in the floor of the dorsal aorta (DA). Despite being integral to arteries, it is controversial whether HE and arterial endothelium share a common lineage. Here, we present a transgenic zebrafish runx1 reporter line to isolate HE and aortic roof endothelium (ARE)s, excluding non-aortic endothelium. Transcriptomic analysis of these populations identifies Runx1-regulated genes and shows that HE initially expresses arterial markers at similar levels to ARE. Furthermore, runx1 expression depends on prior arterial programming by the Notch ligand dll4. Runx1−/− mutants fail to downregulate arterial genes in the HE, which remains integrated within the DA, suggesting that Runx1 represses the pre-existing arterial programme in HE to allow progression towards the haematopoietic fate. These findings strongly suggest that, in zebrafish, aortic endothelium is a precursor to HE, with potential implications for pluripotent stem cell differentiation protocols for the generation of transplantable HSCs.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 3.1MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41467-019-11423-2
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 10
- Issue:
- 1
- Article number:
- 3577
- Publication date:
- 2019-08-08
- Acceptance date:
- 2019-07-10
- DOI:
- EISSN:
-
2041-1723
- Pmid:
-
31395869
- Language:
-
English
- Pubs id:
-
pubs:1046736
- UUID:
-
uuid:5d2c30d9-562e-4c93-8eb7-6d4ac2ad2aab
- Local pid:
-
pubs:1046736
- Source identifiers:
-
1046736
- Deposit date:
-
2019-09-05
Terms of use
- Copyright holder:
- Bonkhofer et al
- Copyright date:
- 2019
- Notes:
- © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record