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Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta
Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359911/ https://www.ncbi.nlm.nih.gov/pubmed/35902769 http://dx.doi.org/10.1038/s41556-022-00955-3 |
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author | Chandrakanthan, Vashe Rorimpandey, Prunella Zanini, Fabio Chacon, Diego Olivier, Jake Joshi, Swapna Kang, Young Chan Knezevic, Kathy Huang, Yizhou Qiao, Qiao Oliver, Rema A. Unnikrishnan, Ashwin Carter, Daniel R. Lee, Brendan Brownlee, Chris Power, Carl Brink, Robert Mendez-Ferrer, Simon Enikolopov, Grigori Walsh, William Göttgens, Berthold Taoudi, Samir Beck, Dominik Pimanda, John E. |
author_facet | Chandrakanthan, Vashe Rorimpandey, Prunella Zanini, Fabio Chacon, Diego Olivier, Jake Joshi, Swapna Kang, Young Chan Knezevic, Kathy Huang, Yizhou Qiao, Qiao Oliver, Rema A. Unnikrishnan, Ashwin Carter, Daniel R. Lee, Brendan Brownlee, Chris Power, Carl Brink, Robert Mendez-Ferrer, Simon Enikolopov, Grigori Walsh, William Göttgens, Berthold Taoudi, Samir Beck, Dominik Pimanda, John E. |
author_sort | Chandrakanthan, Vashe |
collection | PubMed |
description | Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta–gonad–mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA(+) stromal cells (Mesp1(der) PSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5–E11.5 aorta–gonad–mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1(der) PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1(der) PSCs but not Wnt1(der) PSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta–gonad–mesonephros Mesp1(der) PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium. |
format | Online Article Text |
id | pubmed-9359911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93599112022-08-10 Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta Chandrakanthan, Vashe Rorimpandey, Prunella Zanini, Fabio Chacon, Diego Olivier, Jake Joshi, Swapna Kang, Young Chan Knezevic, Kathy Huang, Yizhou Qiao, Qiao Oliver, Rema A. Unnikrishnan, Ashwin Carter, Daniel R. Lee, Brendan Brownlee, Chris Power, Carl Brink, Robert Mendez-Ferrer, Simon Enikolopov, Grigori Walsh, William Göttgens, Berthold Taoudi, Samir Beck, Dominik Pimanda, John E. Nat Cell Biol Article Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta–gonad–mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA(+) stromal cells (Mesp1(der) PSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5–E11.5 aorta–gonad–mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1(der) PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1(der) PSCs but not Wnt1(der) PSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta–gonad–mesonephros Mesp1(der) PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium. Nature Publishing Group UK 2022-07-28 2022 /pmc/articles/PMC9359911/ /pubmed/35902769 http://dx.doi.org/10.1038/s41556-022-00955-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access 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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chandrakanthan, Vashe Rorimpandey, Prunella Zanini, Fabio Chacon, Diego Olivier, Jake Joshi, Swapna Kang, Young Chan Knezevic, Kathy Huang, Yizhou Qiao, Qiao Oliver, Rema A. Unnikrishnan, Ashwin Carter, Daniel R. Lee, Brendan Brownlee, Chris Power, Carl Brink, Robert Mendez-Ferrer, Simon Enikolopov, Grigori Walsh, William Göttgens, Berthold Taoudi, Samir Beck, Dominik Pimanda, John E. Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title | Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title_full | Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title_fullStr | Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title_full_unstemmed | Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title_short | Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
title_sort | mesoderm-derived pdgfra(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359911/ https://www.ncbi.nlm.nih.gov/pubmed/35902769 http://dx.doi.org/10.1038/s41556-022-00955-3 |
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