A multistep computational approach reveals a neuro-mesenchymal cell population in the embryonic hematopoietic stem cell niche
Olivera Miladinovic
(1, 2)
,
Pierre-Yves Canto
(1, 2)
,
Claire Pouget
(3)
,
Olivier Piau
(1, 2, 4, 5)
,
Nevenka Radic
(1, 2)
,
Priscilla Freschu
(1, 2)
,
Alexandre Megherbi
(1, 2)
,
Carla Brujas Prats
(1, 2)
,
Sebastien Jacques
(6, 7)
,
Estelle Hirsinger
(1, 2)
,
Audrey Geeverding
(8, 2)
,
Sylvie Dufour
(9)
,
Laurence Petit
(1, 2)
,
Michele Souyri
(10)
,
Trista North
(11, 12)
,
Hervé Isambert
(13)
,
David Traver
(3)
,
Thierry Jaffredo
(1, 2)
,
Pierre Charbord
(1, 2)
,
Charles Durand
(1, 2)
1
LBD -
Laboratoire de Biologie du Développement [IBPS]
2 SU - Sorbonne Université
3 UC San Diego - University of California [San Diego]
4 CRSA - Centre de Recherche Saint-Antoine
5 IUC - Institut Universitaire de Cancérologie [Sorbonne Université]
6 IC UM3 (UMR 8104 / U1016) - Institut Cochin
7 GENOM'IC - Plateforme de genomique
8 IBPS-ME - Microscopie Electronique [IBPS]
9 IMRB - Institut Mondor de Recherche Biomédicale
10 (UMR_S1131 / U1131) - Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris]
11 Boston Children's Hospital
12 HMS - Harvard Medical School [Boston]
13 PCC - Physique des Cellules et Cancer = Physics of Cells and Cancer
2 SU - Sorbonne Université
3 UC San Diego - University of California [San Diego]
4 CRSA - Centre de Recherche Saint-Antoine
5 IUC - Institut Universitaire de Cancérologie [Sorbonne Université]
6 IC UM3 (UMR 8104 / U1016) - Institut Cochin
7 GENOM'IC - Plateforme de genomique
8 IBPS-ME - Microscopie Electronique [IBPS]
9 IMRB - Institut Mondor de Recherche Biomédicale
10 (UMR_S1131 / U1131) - Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris]
11 Boston Children's Hospital
12 HMS - Harvard Medical School [Boston]
13 PCC - Physique des Cellules et Cancer = Physics of Cells and Cancer
Nevenka Radic
- Fonction : Auteur
Estelle Hirsinger
- Fonction : Auteur
- PersonId : 181505
- IdHAL : estelle-hirsinger
- ORCID : 0000-0002-5256-7741
- IdRef : 253122945
Audrey Geeverding
- Fonction : Auteur
- PersonId : 183798
- IdHAL : audrey-geeverding
- ORCID : 0000-0002-0208-0302
Thierry Jaffredo
- Fonction : Auteur
- PersonId : 12859
- IdHAL : thierry-jaffredo
- ORCID : 0000-0002-8724-3261
- IdRef : 097655082
Pierre Charbord
- Fonction : Auteur
- PersonId : 1382964
- ORCID : 0000-0002-2254-3300
Charles Durand
- Fonction : Auteur
- PersonId : 1380986
- ORCID : 0000-0002-1970-0467
- IdRef : 225654717
Résumé
ABSTRACT The first hematopoietic stem and progenitor cells (HSPCs) emerge in the Aorta-Gonad-Mesonephros (AGM) region of the mid-gestation mouse embryo. However, the precise nature of their supportive mesenchymal microenvironment remains largely unexplored. Here, we profiled transcriptomes of laser micro-dissected aortic tissues at three developmental stages and individual AGM cells. Computational analyses allowed the identification of several cell subpopulations within the E11.5 AGM mesenchyme, with the presence of a yet unidentified subpopulation characterized by the dual expression of genes implicated in adhesive or neuronal functions. We confirmed the identity of this cell subset as a neuro-mesenchymal population, through morphological and lineage tracing assays. Loss of function in the zebrafish confirmed that Decorin, a characteristic extracellular matrix component of the neuro-mesenchyme, is essential for HSPC development. We further demonstrated that this cell population is not merely derived from the neural crest, and hence, is a bona fide novel subpopulation of the AGM mesenchyme.