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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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