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Identification of a Pro-angiogenic Functional Role for FSP1-positive Fibroblast Subtype in Wound Healing

dc.contributor.authorSaraswati, Sarika
dc.contributor.authorMarrow, Stephanie M. W.
dc.contributor.authorWatch, Lester A.
dc.contributor.authorYoung, Pampee P.
dc.identifier.citationSaraswati, Sarika, Marrow, Stephanie M. W., Watch, Lester A., Young, Pampee,, 2019/07/09, Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing, Nature Communications, 10, 1.en_US
dc.description.abstractFibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or alpha SMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP(+) cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic alpha SMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.en_US
dc.description.sponsorshipThe authors want to thank Drs. Jeffrey M. Davidson and Hind Lal for careful reading of the manuscript and their critical feedback. We also want to thank David K. Flaherty from Vanderbilt Flow Cytometry Shared Resource and Dr. Shan Wang from Division of Rheumatology and Immunology at the Vanderbilt University Medical Center for their input in flow cytometry data analysis and presentation. We thank Drs. William E. Lawson and Eric Neilson for providing FSP1-GFP mice and Ivo Kalajzic for the gift of aSMA-GFP mice. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Number R01GM118300 (S.S.), National Institute of Biomedical Imaging and Bioengineering of the NIH under Award Number R21EB019509 (P.P.Y.), National Blood Foundation Grant (S.S.), and Scientist Development Grant of the American Heart Association under Award Number 17SDG33630187 (S.S.). Confocal imaging and electron microscopy analyses were performed in part using the VU Cell Imaging Shared Resource (supported by NIH grants CA68485, DK20593, DK58404, DK59637, and EY08126). Flow cytometry analyses were performed at the VMC Flow Cytometry Shared Resource which is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). The Vanderbilt VANTAGE Core provided technical assistance for RNA sequencing work. VANTAGE is supported in part by CTSA Grant (5UL1 RR024975-03), the Vanderbilt Ingram Cancer Center (P30 CA68485), the Vanderbilt Vision Center (P30 EY08126), and NIH/NCRR (G20 RR030956).en_US
dc.rightsThis 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.
dc.subjectTransforming growth-factor-beta 1en_US
dc.subjectmyofibroblast differentiationen_US
dc.subjectcardiac fibroblastsen_US
dc.subjectprogenitor cellsen_US
dc.titleIdentification of a Pro-angiogenic Functional Role for FSP1-positive Fibroblast Subtype in Wound Healingen_US

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