Renin-angiotensin system is involved in embryonic emergence of hematopoietic stem/progenitor cells.

Fiche publication

Date publication

janvier 2021

Journal

Stem cells (Dayton, Ohio)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr FREUND Jean-Noël , Dr TAVIAN Manuela , Dr GACHET Christian

Tous les auteurs :
Julien E, Biasch K, El Omar R, Freund JN, Gachet C, Lanza F, Tavian M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33480126

Résumé

Angiotensin-converting enzyme (ACE), a key element of the renin-angiotensin system (RAS), has recently been identified as a new marker of both adult and embryonic human hematopoietic stem/progenitor cells (HSPCs). However, whether a full renin-angiotensin pathway is locally present during the hematopoietic emergence is still an open question. In the present study, we show that this enzyme is expressed by hematopoietic progenitors in the developing mouse embryo. Furthermore, ACE and the other elements of RAS-namely angiotensinogen, renin, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors-are expressed in the paraaortic splanchnopleura (P-Sp) and in its derivative, the aorta-gonad-mesonephros region, both in human and mouse embryos. Their localization is compatible with the existence of a local autocrine and/or paracrine RAS in these hemogenic sites. In vitro perturbation of the RAS by administration of a specific AT1 receptor antagonist inhibits almost totally the generation of blood CD45-positive cells from dissected P-Sp, implying that angiotensin II signaling is necessary for the emergence of hematopoietic cells. Conversely, addition of exogenous angiotensin II peptide stimulates hematopoiesis in culture, with an increase in the number of immature c-Kit CD41 CD31 CD45 hematopoietic progenitors, compared to the control. These results highlight a novel role of local-RAS during embryogenesis, suggesting that angiotensin II, via activation of AT1 receptor, promotes the emergence of undifferentiated hematopoietic progenitors. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Self-renewing multipotent hematopoietic stem cells are first generated inside the developing embryo as clusters of cells emerging associated with the ventral side of the aortic endothelium. The present study shows that a local active renin-angiotensin system exists in this hemogenic site and contributes to the blood generation. Angiotensin II-signaling, via activation of type 1 receptor, increases the emergence of undifferentiated hematopoietic progenitors inside the embryo.