Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency

Abstract Fibroblast reprogramming offers the potential for myocardial regeneration via in situ cell transdifferentiation. We explored a novel strategy leveraging endothelial cell plasticity to enhance reprogramming efficiency. Rat cardiac endothelial cells and fibroblasts were treated with Gata4, Me...

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Autores principales:	Megumi Mathison, Deepthi Sanagasetti, Vivek P. Singh, Aarthi Pugazenthi, Jaya Pratap Pinnamaneni, Christopher T. Ryan, Jianchang Yang, Todd K. Rosengart
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd218c69e5e94d91a0439e753722da4a
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spelling	oai:doaj.org-article:dd218c69e5e94d91a0439e753722da4a2021-11-21T12:20:31ZFibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency10.1038/s41598-021-02056-x2045-2322https://doaj.org/article/dd218c69e5e94d91a0439e753722da4a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02056-xhttps://doaj.org/toc/2045-2322Abstract Fibroblast reprogramming offers the potential for myocardial regeneration via in situ cell transdifferentiation. We explored a novel strategy leveraging endothelial cell plasticity to enhance reprogramming efficiency. Rat cardiac endothelial cells and fibroblasts were treated with Gata4, Mef2c, and Tbx5 (GMT) to assess the cardio-differentiation potential of these cells. The endothelial cell transdifferentiation factor ETV2 was transiently over-expressed in fibroblasts followed by GMT treatment to assess “trans-endothelial” cardio-differentiation. Endothelial cells treated with GMT generated more cTnT+ cells than did cardiac fibroblasts (13% ± 2% vs 4% ± 0.5%, p < 0.01). Cardiac fibroblasts treated with ETV2 demonstrated increased endothelial cell markers, and when then treated with GMT yielded greater prevalence of cells expressing cardiomyocyte markers including cTnT than did fibroblasts treated with GMT or ETV2 (10.3% ± 0.2% vs 1.7% ± 0.06% and 0.6 ± 0.03, p < 0.01). Rat cardiac fibroblasts treated with GMT + ETV2 demonstrated calcium transients upon electrical stimulation and contractility synchronous with surrounding neonatal cardiomyocytes, whereas cells treated with GMT or ETV2 alone failed to contract in co-culture experiments. Human cardiac fibroblasts treated with ETV2 and then GMT likewise demonstrated greater prevalence of cTnT expression than did cells treated with GMT alone (2.8-fold increase, p < 0.05). Cardiac fibroblast transitioning through a trans-endothelial state appears to enhance cardio-differentiation by enhancing fibroblast plasticity.Megumi MathisonDeepthi SanagasettiVivek P. SinghAarthi PugazenthiJaya Pratap PinnamaneniChristopher T. RyanJianchang YangTodd K. RosengartNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megumi Mathison Deepthi Sanagasetti Vivek P. Singh Aarthi Pugazenthi Jaya Pratap Pinnamaneni Christopher T. Ryan Jianchang Yang Todd K. Rosengart Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
description	Abstract Fibroblast reprogramming offers the potential for myocardial regeneration via in situ cell transdifferentiation. We explored a novel strategy leveraging endothelial cell plasticity to enhance reprogramming efficiency. Rat cardiac endothelial cells and fibroblasts were treated with Gata4, Mef2c, and Tbx5 (GMT) to assess the cardio-differentiation potential of these cells. The endothelial cell transdifferentiation factor ETV2 was transiently over-expressed in fibroblasts followed by GMT treatment to assess “trans-endothelial” cardio-differentiation. Endothelial cells treated with GMT generated more cTnT+ cells than did cardiac fibroblasts (13% ± 2% vs 4% ± 0.5%, p < 0.01). Cardiac fibroblasts treated with ETV2 demonstrated increased endothelial cell markers, and when then treated with GMT yielded greater prevalence of cells expressing cardiomyocyte markers including cTnT than did fibroblasts treated with GMT or ETV2 (10.3% ± 0.2% vs 1.7% ± 0.06% and 0.6 ± 0.03, p < 0.01). Rat cardiac fibroblasts treated with GMT + ETV2 demonstrated calcium transients upon electrical stimulation and contractility synchronous with surrounding neonatal cardiomyocytes, whereas cells treated with GMT or ETV2 alone failed to contract in co-culture experiments. Human cardiac fibroblasts treated with ETV2 and then GMT likewise demonstrated greater prevalence of cTnT expression than did cells treated with GMT alone (2.8-fold increase, p < 0.05). Cardiac fibroblast transitioning through a trans-endothelial state appears to enhance cardio-differentiation by enhancing fibroblast plasticity.
format	article
author	Megumi Mathison Deepthi Sanagasetti Vivek P. Singh Aarthi Pugazenthi Jaya Pratap Pinnamaneni Christopher T. Ryan Jianchang Yang Todd K. Rosengart
author_facet	Megumi Mathison Deepthi Sanagasetti Vivek P. Singh Aarthi Pugazenthi Jaya Pratap Pinnamaneni Christopher T. Ryan Jianchang Yang Todd K. Rosengart
author_sort	Megumi Mathison
title	Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
title_short	Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
title_full	Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
title_fullStr	Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
title_full_unstemmed	Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
title_sort	fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dd218c69e5e94d91a0439e753722da4a
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Fibroblast transition to an endothelial “trans” state improves cell reprogramming efficiency

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