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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 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.

SUBMITTER: Sa da Bandeira D

PROVIDER: S-EPMC9638014 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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PDGFRβ<sup>+</sup> cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny.

Sá da Bandeira Diana D Kilpatrick Alastair Morris AM Marques Madalena M Gomez-Salazar Mario M Ventura Telma T Gonzalez Zaniah Nashira ZN Stefancova Dorota D Rossi Fiona F Vermeren Matthieu M Vink Chris Sebastiaan CS Beltran Mariana M Henderson Neil Cowan NC Jung Bongnam B van der Linden Reinier R van de Werken Harmen Jan George HJG van Ijcken Wilfred F J WFJ Betsholtz Christer C Forbes Stuart John SJ Cuervo Henar H Crisan Mihaela M

Cell reports 20220701 3

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- ...[more]

PMID: 35858557

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Project description:The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1)+CD133+ hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung. We also established a highly metastatic MDA-MB-435s (MDA-MB-435s-HM) cell line from the mouse model. Changes in protein profiles in different culture conditions were investigated by protein microarray analysis. The levels of CXC chemokine ligand 16, interleukin (IL)-2Rα, IL-2Rγ, matrix metalloproteinase (MMP)-1, MMP-9, platelet-derived growth factor receptor (PDGFR)-α, stromal cell-derived factor (SDF)-1α, transforming growth factor (TGF)-β, platelet endothelial cell adhesion molecule (PECAM)-1 and vascular endothelial (VE)-cadherin were significantly greater (> fivefold) in the culture medium from MDA-MB-435s-HM cells than in that from MDA-MB-435s cells. Moreover, the levels of MMP-9, PDGFR-α, and PECAM-1 were significantly greater in the co-culture medium of MDA-MB-435s-HM cells and CD133+ HPCs than in that from MDA-MB-435s-HM cells. Differentially expressed proteins were validated by enzyme-linked immunosorbent assay, and expression of their transcripts was confirmed by quantitative real-time polymerase chain reaction. Moreover, inhibition of MMP-9, PDGFR-α, and PECAM-1 by their specific inhibitors or antibodies significantly decreased cell migration, delayed lung metastasis, and decreased recruitment of VEGFR1+CD133+ HPCs into lung. Intra-hepatic growth of HPCs enhanced the invasive growth of MDA-MB-435s-HM cells in the liver. Our data indicate that VEGFR1+CD133+ HPCs contribute to lung metastasis.

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

Publications

PDGFRβ<sup>+</sup> cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny.

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Dataset Information

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

Publications

PDGFRβ<sup>+</sup> cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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