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Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling

Pulmonary endothelial progenitor cells (EPCs) are critical for neonatal lung angiogenesis and represent a subset of general capillary cells (gCAPs). Molecular mechanisms through which EPCs stimulate lung angiogenesis are unknown. Herein, we used single-cell RNA sequencing to identify the BMP9/ACVRL1...

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Autores principales: Wang, Guolun, Wen, Bingqiang, Deng, Zicheng, Zhang, Yufang, Kolesnichenko, Olena A., Ustiyan, Vladimir, Pradhan, Arun, Kalin, Tanya V., Kalinichenko, Vladimir V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019054/
https://www.ncbi.nlm.nih.gov/pubmed/35440116
http://dx.doi.org/10.1038/s41467-022-29746-y
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author Wang, Guolun
Wen, Bingqiang
Deng, Zicheng
Zhang, Yufang
Kolesnichenko, Olena A.
Ustiyan, Vladimir
Pradhan, Arun
Kalin, Tanya V.
Kalinichenko, Vladimir V.
author_facet Wang, Guolun
Wen, Bingqiang
Deng, Zicheng
Zhang, Yufang
Kolesnichenko, Olena A.
Ustiyan, Vladimir
Pradhan, Arun
Kalin, Tanya V.
Kalinichenko, Vladimir V.
author_sort Wang, Guolun
collection PubMed
description Pulmonary endothelial progenitor cells (EPCs) are critical for neonatal lung angiogenesis and represent a subset of general capillary cells (gCAPs). Molecular mechanisms through which EPCs stimulate lung angiogenesis are unknown. Herein, we used single-cell RNA sequencing to identify the BMP9/ACVRL1/SMAD1 pathway signature in pulmonary EPCs. BMP9 receptor, ACVRL1, and its downstream target genes were inhibited in EPCs from Foxf1(WT/S52F) mutant mice, a model of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Expression of ACVRL1 and its targets were reduced in lungs of ACDMPV subjects. Inhibition of FOXF1 transcription factor reduced BMP9/ACVRL1 signaling and decreased angiogenesis in vitro. FOXF1 synergized with ETS transcription factor FLI1 to activate ACVRL1 promoter. Nanoparticle-mediated silencing of ACVRL1 in newborn mice decreased neonatal lung angiogenesis and alveolarization. Treatment with BMP9 restored lung angiogenesis and alveolarization in ACVRL1-deficient and Foxf1(WT/S52F) mice. Altogether, EPCs promote neonatal lung angiogenesis and alveolarization through FOXF1-mediated activation of BMP9/ACVRL1 signaling.
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spelling pubmed-90190542022-04-28 Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling Wang, Guolun Wen, Bingqiang Deng, Zicheng Zhang, Yufang Kolesnichenko, Olena A. Ustiyan, Vladimir Pradhan, Arun Kalin, Tanya V. Kalinichenko, Vladimir V. Nat Commun Article Pulmonary endothelial progenitor cells (EPCs) are critical for neonatal lung angiogenesis and represent a subset of general capillary cells (gCAPs). Molecular mechanisms through which EPCs stimulate lung angiogenesis are unknown. Herein, we used single-cell RNA sequencing to identify the BMP9/ACVRL1/SMAD1 pathway signature in pulmonary EPCs. BMP9 receptor, ACVRL1, and its downstream target genes were inhibited in EPCs from Foxf1(WT/S52F) mutant mice, a model of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Expression of ACVRL1 and its targets were reduced in lungs of ACDMPV subjects. Inhibition of FOXF1 transcription factor reduced BMP9/ACVRL1 signaling and decreased angiogenesis in vitro. FOXF1 synergized with ETS transcription factor FLI1 to activate ACVRL1 promoter. Nanoparticle-mediated silencing of ACVRL1 in newborn mice decreased neonatal lung angiogenesis and alveolarization. Treatment with BMP9 restored lung angiogenesis and alveolarization in ACVRL1-deficient and Foxf1(WT/S52F) mice. Altogether, EPCs promote neonatal lung angiogenesis and alveolarization through FOXF1-mediated activation of BMP9/ACVRL1 signaling. Nature Publishing Group UK 2022-04-19 /pmc/articles/PMC9019054/ /pubmed/35440116 http://dx.doi.org/10.1038/s41467-022-29746-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Guolun
Wen, Bingqiang
Deng, Zicheng
Zhang, Yufang
Kolesnichenko, Olena A.
Ustiyan, Vladimir
Pradhan, Arun
Kalin, Tanya V.
Kalinichenko, Vladimir V.
Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title_full Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title_fullStr Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title_full_unstemmed Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title_short Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling
title_sort endothelial progenitor cells stimulate neonatal lung angiogenesis through foxf1-mediated activation of bmp9/acvrl1 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019054/
https://www.ncbi.nlm.nih.gov/pubmed/35440116
http://dx.doi.org/10.1038/s41467-022-29746-y
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