Stem cells
| Autor: | Jean-Noël Freund, Reine El Omar, Manuela Tavian, Emmanuelle Julien, Christian Gachet, François Lanza, Katia Biasch |
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| Přispěvatelé: | Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), ANR-14-CE11-0008,ACEBLOOD,La Spécification hématopoïétique dans l'embryon humain: vers de novo génération de cellules souches hématopoïétiques(2014), PIET, Marie-Helene, Appel à projets générique - La Spécification hématopoïétique dans l'embryon humain: vers de novo génération de cellules souches hématopoïétiques - - ACEBLOOD2014 - ANR-14-CE11-0008 - Appel à projets générique - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Angiotensinogen embryo renin-angiotensin system Peptidyl-Dipeptidase A Biology Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Mice 03 medical and health sciences 0302 clinical medicine angiotensin-converting enzyme hematopoietic stem progenitor cell Renin Animals Humans Progenitor cell hemogenic endothelium Aorta Hemogenic endothelium Angiotensin II receptor type 1 Sciences du Vivant [q-bio]/Biologie du développement Angiotensin II Stem Cells Hematopoietic Stem Cell Transplantation Gene Expression Regulation Developmental Angiotensin-converting enzyme Cell Biology Hematopoietic Stem Cells Embryonic stem cell hematopoiesis Cell biology [SDV] Life Sciences [q-bio] Haematopoiesis 030104 developmental biology biology.protein Leukocyte Common Antigens Molecular Medicine Stem cell Peptides 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | STEM CELLS STEM CELLS, 2021, 39 (5), pp.636-649. ⟨10.1002/stem.3339⟩ |
| ISSN: | 1066-5099 |
| DOI: | 10.1002/stem.3339⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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