Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
<p>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 <em>r...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2019
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| _version_ | 1797070918115131392 |
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| author | Bonkhofer, F Rispoli, R Pinheiro, P Krecsmarik, M Schneider-Swales, J Tsang, I De Bruijn, M Monteiro, R Peterkin, T Patient, R |
| author_facet | Bonkhofer, F Rispoli, R Pinheiro, P Krecsmarik, M Schneider-Swales, J Tsang, I De Bruijn, M Monteiro, R Peterkin, T Patient, R |
| author_sort | Bonkhofer, F |
| collection | OXFORD |
| description | <p>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 <em>runx1</em> 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, <em>runx1</em> expression depends on prior arterial programming by the Notch ligand <em>dll4</em>. Runx1<sup>−/−</sup> 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.</p> |
| first_indexed | 2024-03-06T22:45:56Z |
| format | Journal article |
| id | oxford-uuid:5d2c30d9-562e-4c93-8eb7-6d4ac2ad2aab |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:45:56Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:5d2c30d9-562e-4c93-8eb7-6d4ac2ad2aab2022-03-26T17:32:48ZBlood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endotheliumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5d2c30d9-562e-4c93-8eb7-6d4ac2ad2aabEnglishSymplectic Elements at OxfordNature Research2019Bonkhofer, FRispoli, RPinheiro, PKrecsmarik, MSchneider-Swales, JTsang, IDe Bruijn, MMonteiro, RPeterkin, TPatient, R<p>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 <em>runx1</em> 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, <em>runx1</em> expression depends on prior arterial programming by the Notch ligand <em>dll4</em>. Runx1<sup>−/−</sup> 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.</p> |
| spellingShingle | Bonkhofer, F Rispoli, R Pinheiro, P Krecsmarik, M Schneider-Swales, J Tsang, I De Bruijn, M Monteiro, R Peterkin, T Patient, R Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title | Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title_full | Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title_fullStr | Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title_full_unstemmed | Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title_short | Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium |
| title_sort | blood stem cell forming haemogenic endothelium in zebrafish derives from arterial endothelium |
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