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

Development. 2024 Apr 1;151(7):dev202614. doi: 10.1242/dev.202614. Epub 2024 Apr 4.


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.

Keywords: Aorta-Gonad-Mesonephros; Gene networks; Hematopoietic stem cells; Laser microdissection; Mesenchyme; Niche.

MeSH terms

  • Animals
  • Embryo, Mammalian
  • Gonads
  • Hematopoiesis
  • Hematopoietic Stem Cells / metabolism
  • Mesenchymal Stem Cells*
  • Mesonephros
  • Mice
  • Zebrafish* / genetics