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Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells
Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth fac...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928864/ https://www.ncbi.nlm.nih.gov/pubmed/31801200 http://dx.doi.org/10.3390/ijms20236037 |
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author | Jennbacken, Karin Wågberg, Fredrik Karlsson, Ulla Eriksson, Jerry Magnusson, Lisa Chimienti, Marjorie Ricchiuto, Piero Bernström, Jenny Ding, Mei Ross-Thriepland, Douglas Xue, Yafeng Peiris, Diluka Aastrup, Teodor Tegel, Hanna Hober, Sophia Sivertsson, Åsa Uhlén, Mathias Strömstedt, Per-Erik Davies, Rick Holmberg Schiavone, Lovisa |
author_facet | Jennbacken, Karin Wågberg, Fredrik Karlsson, Ulla Eriksson, Jerry Magnusson, Lisa Chimienti, Marjorie Ricchiuto, Piero Bernström, Jenny Ding, Mei Ross-Thriepland, Douglas Xue, Yafeng Peiris, Diluka Aastrup, Teodor Tegel, Hanna Hober, Sophia Sivertsson, Åsa Uhlén, Mathias Strömstedt, Per-Erik Davies, Rick Holmberg Schiavone, Lovisa |
author_sort | Jennbacken, Karin |
collection | PubMed |
description | Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naïve cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair. |
format | Online Article Text |
id | pubmed-6928864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69288642019-12-26 Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells Jennbacken, Karin Wågberg, Fredrik Karlsson, Ulla Eriksson, Jerry Magnusson, Lisa Chimienti, Marjorie Ricchiuto, Piero Bernström, Jenny Ding, Mei Ross-Thriepland, Douglas Xue, Yafeng Peiris, Diluka Aastrup, Teodor Tegel, Hanna Hober, Sophia Sivertsson, Åsa Uhlén, Mathias Strömstedt, Per-Erik Davies, Rick Holmberg Schiavone, Lovisa Int J Mol Sci Article Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naïve cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair. MDPI 2019-11-30 /pmc/articles/PMC6928864/ /pubmed/31801200 http://dx.doi.org/10.3390/ijms20236037 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jennbacken, Karin Wågberg, Fredrik Karlsson, Ulla Eriksson, Jerry Magnusson, Lisa Chimienti, Marjorie Ricchiuto, Piero Bernström, Jenny Ding, Mei Ross-Thriepland, Douglas Xue, Yafeng Peiris, Diluka Aastrup, Teodor Tegel, Hanna Hober, Sophia Sivertsson, Åsa Uhlén, Mathias Strömstedt, Per-Erik Davies, Rick Holmberg Schiavone, Lovisa Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title | Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title_full | Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title_fullStr | Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title_full_unstemmed | Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title_short | Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells |
title_sort | phenotypic screen with the human secretome identifies fgf16 as inducing proliferation of ipsc-derived cardiac progenitor cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928864/ https://www.ncbi.nlm.nih.gov/pubmed/31801200 http://dx.doi.org/10.3390/ijms20236037 |
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