A multistep computational approach reveals a neuro-mesenchymal cell population in the embryonic hematopoietic stem cell niche

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Miladinovic, Olivera | Canto, Pierre-Yves | Pouget, Claire | Piau, Olivier | Radic, Nevenka | Freschu, Priscilla | Megherbi, Alexandre | Brujas Prats, Carla | Jacques, Sebastien | Hirsinger, Estelle | Geeverding, Audrey | Dufour, Sylvie | Petit, Laurence | Souyri, Michele | North, Trista | Isambert, Hervé | Traver, David | Jaffredo, Thierry | Charbord, Pierre | Durand, Charles

Edité par CCSD ; Company of Biologists -

International audience. 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.

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