PDGFRβ ⁺ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Summary

Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFRβ is involved. Here, we show that PDGFRβ is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFRβ ⁺ cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFRβ ⁺ embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.

Graphical abstract

Highlights

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  PDGFRβ deletion affects hematopoietic development in the AGM in vivo

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  The transcriptome and hematopoietic support of the PDGFRβ-KO niche are altered

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  The osteogenic gene profile and differentiation of KO AGM MSCs are affected

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  PDGFRβ ⁺ early embryonic precursors contribute to EC and HSPC lineages in vivo

Abstract

Sá da Bandeira et al. find that PDGFRβ, expressed in the AGM hematopoietic microenvironment, controls HSPCs. By RNA sequencing, hematopoietic assays, and lineage tracing, they show that PDGFRβ has a dual role: it is required in the AGM hematopoietic niche and marks early precursors of a subset of ECs and HSPCs.