A neuro-mesenchymal cell subpopulation characterises the subaortic hematopoietic stem cell niche
The first hematopoietic stem and progenitor cells (HSPCs) emerge in the embryonic dorsal aorta of midgestation mouse embryo, but the precise nature of the supportive microenvironment remains largely unexplored. To address this question, we designed a laser microdissection-based approach to isolate the dorsal and ventral tissues of the aorta at three distinct developmental stages harboring HSPCs. Bulk and single cell transcriptomics combined with computational analyses disclosed a large mesenchymal cell population in the E11.5 subaortic tissue including a subset expressing interconnected genes implicated in adhesive and neuronal functions. In vivo lineage tracing showed that this subset does not derive from neural crest cells. Histological and functional studies validated our strategy and revealed that Decorin, and Tenascin C, two components of the extracellular matrix (ECM), are essential for HSPC development. Together, our study identifies a yet unrecognized subaortic mesenchymal cell population and underscores the critical role of the ECM on embryonic HSPCs. Overall design: E11.5 AGMs were collected, dissociated by enzymatic treatment and analyzed by the Chromium 10X Genomics v3.1 technology.