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

Williamson, Anna E.; Liyanage, S; Hassanshahi, M; Dona, MSI; Toledo-Flores, D; Tran, DXA; Dimasi, C; Schwarz, N; Fernando, S; Salagaras, T; Long, A; Kazenwadel, J; Harvey, NL; Drummond, Grant; Vinh, Antony; Chandrakanthan, V; Misra, A; Neufeld, Z; Tan, JTM; Martelotto, L; Polo, JM; Bonder, CS; Pinto, Ruvantha; Sharma, Shiwani; Nicholls, SJ; Bursill, CA; J. Psaltis, Peter

doi:10.26181/27002599.v1

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

journal contribution

posted on 2024-09-12, 07:09 authored by Anna E. Williamson, S Liyanage, M Hassanshahi, MSI Dona, D Toledo-Flores, DXA Tran, C Dimasi, N Schwarz, S Fernando, T Salagaras, A Long, J Kazenwadel, NL Harvey, Grant DrummondGrant Drummond, Antony VinhAntony Vinh, V Chandrakanthan, A Misra, Z Neufeld, JTM Tan, L Martelotto, JM Polo, CS Bonder, Ruvantha PintoRuvantha Pinto, Shiwani Sharma, SJ Nicholls, CA Bursill, Peter J. Psaltis

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.

Funding

This work was supported by the National Health and Medical Research Council of Australia [PG 1086796, IG 2001541, PRF 1111630 to S.J.N., CDF 1161506 to P.J.P.]; the National Heart Foundation of Australia [VG 102981, Lin Huddleston Fellowship to C.A.B., FLF 100412, 102056 and 106656 to P.J.P.]; and the Royal Australasian College of Physicians.

History

Publication Date

2024-08-17

Journal

Nature Communications

Volume

15

Article Number

7097

Pagination

21p.

Publisher

Springer Nature

ISSN

2041-1723

Rights Statement

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