A multistep computational approach reveals a neuro-mesenchymal cell population in the embryonic hematopoietic stem cell niche
Olivera Miladinović, Pierre‐Yves Canto, Claire Pouget, Olivier Piau, Nevenka Radic, Priscilla Freschu, Alexandre Megherbi, Carla Brujas Prats, Sébastien Jacques, Estelle Hirsinger, Audrey Geeverding, Sylvie Dufour, Laurence Petit, Michèle Souyri, Trista E. North, Hervé Isambert, David Traver, Thierry Jaffredo, Pierre Charbord, Charles Durand
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.