PUBLICATION

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

Authors
Miladinovic, O., Canto, P.Y., Pouget, C., Piau, O., Radic, N., Freschu, P., Megherbi, A., Prats, C.B., Jacques, S., Hirsinger, E., Geeverding, A., Dufour, S., Petit, L., Souyri, M., North, T., Isambert, H., Traver, D., Jaffredo, T., Charbord, P., Durand, C.
ID
ZDB-PUB-240308-3
Date
2024
Source
Development (Cambridge, England)   151(7): (Journal)
Registered Authors
Hirsinger, Estelle, North, Trista, Traver, David
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
PubMed
38451068 Full text @ Development
Abstract
The first hematopoietic stem and progenitor cells (HSPCs) emerge in the Aorta-Gonad-Mesonephros (AGM) region of 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 identifying several cell subpopulations within the embryonic day 11.5 AGM mesenchyme, with the remarkable 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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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping