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

doi:10.1016/j.celrep.2022.111114

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 journal › Article › peer-review

Abstract / Description of output

Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires
HSC specification signals from the surrounding microenvironment. In zebrafish, PDGFB/
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 language	English
Journal	Cell Reports
Volume	40
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2022.111114
Publication status	Published - 19 Jul 2022

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10.1016/j.celrep.2022.111114

Sa da Bandeira et al Cell Reports AcceptedAccepted author manuscript, 407 MBLicence: Creative Commons: Attribution (CC-BY)
PIIS2211124722009202Final published version, 9.46 MBLicence: CC BY

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Sá da Bandeira, D., Kilpatrick, A. M., Marques, M., Gomez-Salazar, M., Ventura, T., Gonzalez , Z. N., Stefancova, D., Rossi, F., Vermeren, M., Vink, C. S., Beltran, M., Henderson, N. C., Jung, B., Van Der Linden, R., van de Werken, H. J. G., van IJcken, W. F. J., Betsholtz, C., Forbes, S. J., Cuervo, H., & Crisan, M. (2022). PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny. Cell Reports, 40(3). https://doi.org/10.1016/j.celrep.2022.111114

@article{258fbdaa1b7146ffa63efb88077f21d4,

title = "PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny",

abstract = "Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requiresHSC specification signals from the surrounding microenvironment. In zebrafish, PDGFB/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and isrequired in the HSC specification niche. Little is known about murine HSPC specification invivo and whether PDGF-B/PDGFRβ is involved. Here we show that PDGFRβ is expressed indistinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and itsdeletion impairs hematopoiesis. We demonstrate that PDGFRβ+ cells play a dual role in murinehematopoiesis. 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 findingsprovide crucial information for the controlled production of HSPCs in vitro.",

author = "{S{\'a} da Bandeira}, Diana and Kilpatrick, {Alastair Morris} and Madalena Marques and Mario Gomez-Salazar and Telma Ventura and Gonzalez, {Zaniah Nashira} and Dorota Stefancova and Fiona Rossi and Matthieu Vermeren and Vink, {Chris Sebastiaan} and Mariana Beltran and Henderson, {Neil Cowan} and Bongnam Jung and {Van Der Linden}, Reinier and {van de Werken}, {Harmen Jan George} and {van IJcken}, {Wilfred F J} and Christer Betsholtz and Forbes, {Stuart John} and Henar Cuervo and Mihaela Crisan",

note = "Funding Information: The authors would like to thank Elaine Dzierzak and Bruno P{\'e}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: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = jul,

day = "19",

doi = "10.1016/j.celrep.2022.111114",

language = "English",

volume = "40",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

}

Sá da Bandeira, D, Kilpatrick, AM, Marques, M, Gomez-Salazar, M, Ventura, T, Gonzalez , ZN, Stefancova, D, Rossi, F, Vermeren, M, Vink, CS, Beltran, M, Henderson, NC, Jung, B, Van Der Linden, R, van de Werken, HJG, van IJcken, WFJ, Betsholtz, C, Forbes, SJ, Cuervo, H & Crisan, M 2022, 'PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny', Cell Reports, vol. 40, no. 3. https://doi.org/10.1016/j.celrep.2022.111114

TY - JOUR

T1 - PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

AU - Sá da Bandeira, Diana

AU - Kilpatrick, Alastair Morris

AU - Marques, Madalena

AU - Gomez-Salazar, Mario

AU - Ventura, Telma

AU - Gonzalez , Zaniah Nashira

AU - Stefancova, Dorota

AU - Rossi, Fiona

AU - Vermeren, Matthieu

AU - Vink, Chris Sebastiaan

AU - Beltran, Mariana

AU - Henderson, Neil Cowan

AU - Jung, Bongnam

AU - Van Der Linden, Reinier

AU - van de Werken, Harmen Jan George

AU - van IJcken, Wilfred F J

AU - Betsholtz, Christer

AU - Forbes, Stuart John

AU - Cuervo, Henar

AU - Crisan, Mihaela

N1 - Funding Information: The authors would like to thank Elaine Dzierzak and Bruno Péault 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)

PY - 2022/7/19

Y1 - 2022/7/19

N2 - Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requiresHSC specification signals from the surrounding microenvironment. In zebrafish, PDGFB/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and isrequired in the HSC specification niche. Little is known about murine HSPC specification invivo and whether PDGF-B/PDGFRβ is involved. Here we show that PDGFRβ is expressed indistinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and itsdeletion impairs hematopoiesis. We demonstrate that PDGFRβ+ cells play a dual role in murinehematopoiesis. 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 findingsprovide crucial information for the controlled production of HSPCs in vitro.

AB - Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requiresHSC specification signals from the surrounding microenvironment. In zebrafish, PDGFB/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and isrequired in the HSC specification niche. Little is known about murine HSPC specification invivo and whether PDGF-B/PDGFRβ is involved. Here we show that PDGFRβ is expressed indistinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and itsdeletion impairs hematopoiesis. We demonstrate that PDGFRβ+ cells play a dual role in murinehematopoiesis. 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 findingsprovide crucial information for the controlled production of HSPCs in vitro.

U2 - 10.1016/j.celrep.2022.111114

DO - 10.1016/j.celrep.2022.111114

M3 - Article

C2 - 35858557

SN - 2211-1247

VL - 40

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

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

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CRM Imaging Facility

Institute for Regeneration and Repair Flow Cytometry Facility

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