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

Diana Sá da Bandeira, Alastair Morris Kilpatrick, Madalena Marques, Mario Gomez-Salazar, Telma Ventura, Zaniah Nashira Gonzalez, Dorota Stefancova, Fiona Rossi, Matthieu Vermeren, Chris Sebastiaan Vink, Mariana Beltran, Neil Cowan Henderson, Bongnam Jung, Reinier van der Linden, Harmen Jan George van de Werken, Wilfred F.J. van Ijcken, Christer Betsholtz, Stuart John Forbes, Henar Cuervo, Mihaela Crisan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number111114
JournalCell Reports
Volume40
Issue number3
DOIs
Publication statusPublished - 19 Jul 2022

Bibliographical note

ACKNOWLEDGMENTS
The authors would like to thank Elaine Dzierzak and Bruno Pe´ ault for comments on the manuscript and our laboratory members for discussion of our
data. We thank James Downing for donating Runx1-IRES-GFP mice and
James Ashmore for bioinformatics advice. We are grateful to staff of the University of Edinburgh imaging, flow cytometry, and animal units for their help,
Edinburgh Genomics for library sequencing, and Edinburgh Compute and
Data Facility for resources provided. We acknowledge the European Hematology Association (EHA) Advance Longterm Fellowship (2882492\R83480), the
Academy of Medical Sciences (AMS) Springboard Award (SBF001\1007),
the Association Francaise contre la Myopathie (AFM) Trampoline Award
(22134/6744359 I190311-2308), the British Heart Foundation (BHF) Research
Excellence Award (REA3) pump-priming grant (RE/18/5/34216), and the University of Edinburgh Wellcome Trust Institutional Strategic Support Fund
(ISSF3, 199MCR/J22739) to M.C. N.C.H. is supported by a Wellcome Trust
Senior Research Fellowship in Clinical Science (219542/Z/19/Z), Medical
Research Council (MRC), Chan Zuckerberg Initiative Seed Network Grant,
and British Heart Foundation (BHF) grants (RM/17/3/33381 and RE/18/5/
34216). C.B. is supported by Swedish Research Council (2015-00550), Swedish Cancer Society (150735), and Knut and Alice Wallenberg Foundation
(2015.0030).

Publisher Copyright: © 2022 The Author(s)

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