Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.

Chandrakanthan, V; Rorimpandey, P; Zanini, F; Chacon, D; Olivier, J; Joshi, S; Kang, YC; Knezevic, K; Huang, Y; Qiao, Q; Oliver, RA; Unnikrishnan, A; Carter, DR; Lee, B; Brownlee, C; Power, C; Brink, R; Mendez-Ferrer, S; Enikolopov, G; Walsh, W; Göttgens, B; Taoudi, S; Beck, D; Pimanda, JE

Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.

Chandrakanthan, V Rorimpandey, P Zanini, F Chacon, D Olivier, J Joshi, S Kang, YC Knezevic, K Huang, Y

Qiao, Q Oliver, RA Unnikrishnan, A Carter, DR Lee, B Brownlee, C Power, C Brink, R Mendez-Ferrer, S Enikolopov, G Walsh, W Göttgens, B Taoudi, S Beck, D Pimanda, JE

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Cell Biol, 2022, 24, (8), pp. 1211-1225
Issue Date:: 2022-08

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Field	Value	Language
dc.contributor.author	Chandrakanthan, V
dc.contributor.author	Rorimpandey, P
dc.contributor.author	Zanini, F
dc.contributor.author	Chacon, D
dc.contributor.author	Olivier, J
dc.contributor.author	Joshi, S
dc.contributor.author	Kang, YC
dc.contributor.author	Knezevic, K
dc.contributor.author	Huang, Y https://orcid.org/0000-0002-7003-3110
dc.contributor.author	Qiao, Q
dc.contributor.author	Oliver, RA
dc.contributor.author	Unnikrishnan, A
dc.contributor.author	Carter, DR
dc.contributor.author	Lee, B
dc.contributor.author	Brownlee, C
dc.contributor.author	Power, C
dc.contributor.author	Brink, R
dc.contributor.author	Mendez-Ferrer, S
dc.contributor.author	Enikolopov, G
dc.contributor.author	Walsh, W
dc.contributor.author	Göttgens, B
dc.contributor.author	Taoudi, S
dc.contributor.author	Beck, D
dc.contributor.author	Pimanda, JE
dc.date.accessioned	2023-04-04T05:27:24Z
dc.date.available	2022-06-06
dc.date.available	2023-04-04T05:27:24Z
dc.date.issued	2022-08
dc.identifier.citation	Nat Cell Biol, 2022, 24, (8), pp. 1211-1225
dc.identifier.issn	1465-7392
dc.identifier.issn	1476-4679
dc.identifier.uri	http://hdl.handle.net/10453/169108
dc.description.abstract	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 (Mesp1der 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 (Wnt1der PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1der PSCs but not Wnt1der 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 Mesp1der PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation	Gilead Sciences Pty Ltd
dc.relation	Cancer Institute NSW
dc.relation	Anthony Rothe Memorial Trust
dc.relation.ispartof	Nat Cell Biol
dc.relation.isbasedon	10.1038/s41556-022-00955-3
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.classification	Developmental Biology
dc.subject.mesh	Animals
dc.subject.mesh	Aorta
dc.subject.mesh	Hemangioblasts
dc.subject.mesh	Hematopoiesis
dc.subject.mesh	Hematopoietic Stem Cells
dc.subject.mesh	Mesoderm
dc.subject.mesh	Mesonephros
dc.subject.mesh	Mice
dc.subject.mesh	Aorta
dc.subject.mesh	Hematopoietic Stem Cells
dc.subject.mesh	Mesoderm
dc.subject.mesh	Mesonephros
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Hematopoiesis
dc.subject.mesh	Hemangioblasts
dc.subject.mesh	Animals
dc.subject.mesh	Aorta
dc.subject.mesh	Hemangioblasts
dc.subject.mesh	Hematopoiesis
dc.subject.mesh	Hematopoietic Stem Cells
dc.subject.mesh	Mesoderm
dc.subject.mesh	Mesonephros
dc.subject.mesh	Mice
dc.title	Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.
dc.type	Journal Article
utslib.citation.volume	24
utslib.location.activity	England
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-04-04T05:27:13Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	24
utslib.citation.issue	8

Abstract:

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 (Mesp1der 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 (Wnt1der PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1der PSCs but not Wnt1der 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 Mesp1der PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.

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http://hdl.handle.net/10453/169108