Discovery of an embryonically derived bipotent population of endothelial-macrophage progenitor cells in postnatal aorta

Anna E. Williamson, Sanuri Liyanage, Mohammadhossein Hassanshahi, Malathi S. I. Dona, Deborah Toledo-Flores, Dang X. A. Tran, Catherine Dimasi, Nisha Schwarz, Sanuja Fernando, Thalia Salagaras, Aaron Long, Jan Kazenwadel, Natasha L. Harvey, Grant R. Drummond, Antony Vinh, Vashe Chandrakanthan, Ashish Misra, Zoltan Neufeld, Joanne T. M. Tan, Luciano Martelotto, Jose M. Polo, Claudine S. Bonder, Alexander R. Pinto, Shiwani Sharma, Stephen J. Nicholls, Christina A. Bursill and Peter J. Psaltis ()
Additional contact information
Anna E. Williamson: South Australian Health and Medical Research Institute
Sanuri Liyanage: South Australian Health and Medical Research Institute
Mohammadhossein Hassanshahi: South Australian Health and Medical Research Institute
Malathi S. I. Dona: Baker Heart and Diabetes Institute
Deborah Toledo-Flores: South Australian Health and Medical Research Institute
Dang X. A. Tran: South Australian Health and Medical Research Institute
Catherine Dimasi: South Australian Health and Medical Research Institute
Nisha Schwarz: South Australian Health and Medical Research Institute
Sanuja Fernando: South Australian Health and Medical Research Institute
Thalia Salagaras: South Australian Health and Medical Research Institute
Aaron Long: South Australian Health and Medical Research Institute
Jan Kazenwadel: University of South Australia and SA Pathology
Natasha L. Harvey: The University of Adelaide
Grant R. Drummond: La Trobe University
Antony Vinh: La Trobe University
Vashe Chandrakanthan: The University of Adelaide
Ashish Misra: University of Sydney and Heart Research Institute
Zoltan Neufeld: The University of Queensland
Joanne T. M. Tan: South Australian Health and Medical Research Institute
Luciano Martelotto: The University of Adelaide
Jose M. Polo: The University of Adelaide
Claudine S. Bonder: University of South Australia and SA Pathology
Alexander R. Pinto: Baker Heart and Diabetes Institute
Shiwani Sharma: South Australian Health and Medical Research Institute
Stephen J. Nicholls: Monash University
Christina A. Bursill: South Australian Health and Medical Research Institute
Peter J. Psaltis: South Australian Health and Medical Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.

Date: 2024
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DOI: 10.1038/s41467-024-51637-7

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