Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro

Abstract Mouse models have been used to provide primary cells to study physiology and pathogenesis of epithelia. However, highly efficient simple approaches to propagate mouse primary epithelial cells remain challenging. Here, we show that pharmacological inhibition of TGF-β signaling enables long-t...

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Autores principales:	Daisuke Suzuki, Filipa Pinto, Makoto Senoo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e45c0d6025d24b75895a7215ab9b5e92
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spelling	oai:doaj.org-article:e45c0d6025d24b75895a7215ab9b5e922021-12-02T15:06:15ZInhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro10.1038/s41598-017-06470-y2045-2322https://doaj.org/article/e45c0d6025d24b75895a7215ab9b5e922017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06470-yhttps://doaj.org/toc/2045-2322Abstract Mouse models have been used to provide primary cells to study physiology and pathogenesis of epithelia. However, highly efficient simple approaches to propagate mouse primary epithelial cells remain challenging. Here, we show that pharmacological inhibition of TGF-β signaling enables long-term expansion of p63+ epithelial progenitor cells in low Ca2+ media without the need of progenitor cell-purification steps or support by a feeder cell layer. We find that TGF-β signaling is operative in mouse primary keratinocytes in conventional cultures as determined by the nuclear Smad2/3 localization. Accordingly, TGF-β signaling inhibition in crude preparations of mouse epidermis robustly increases proliferative capacity of p63+ epidermal progenitor cells, while preserving their ability of differentiation in response to Ca2+ stimulation. Notably, inhibition of TGF-β signaling also enriches and expands other p63+ epithelial progenitor cells in primary crude cultures of multiple epithelia, including the cornea, oral and lingual epithelia, salivary gland, esophagus, thymus, and bladder. We anticipate that this simple and efficient approach will facilitate the use of mouse models for studying a wide range of epithelia by providing highly enriched populations of diverse p63+ epithelial progenitor cells in quantity.Daisuke SuzukiFilipa PintoMakoto SenooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Suzuki Filipa Pinto Makoto Senoo Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
description	Abstract Mouse models have been used to provide primary cells to study physiology and pathogenesis of epithelia. However, highly efficient simple approaches to propagate mouse primary epithelial cells remain challenging. Here, we show that pharmacological inhibition of TGF-β signaling enables long-term expansion of p63+ epithelial progenitor cells in low Ca2+ media without the need of progenitor cell-purification steps or support by a feeder cell layer. We find that TGF-β signaling is operative in mouse primary keratinocytes in conventional cultures as determined by the nuclear Smad2/3 localization. Accordingly, TGF-β signaling inhibition in crude preparations of mouse epidermis robustly increases proliferative capacity of p63+ epidermal progenitor cells, while preserving their ability of differentiation in response to Ca2+ stimulation. Notably, inhibition of TGF-β signaling also enriches and expands other p63+ epithelial progenitor cells in primary crude cultures of multiple epithelia, including the cornea, oral and lingual epithelia, salivary gland, esophagus, thymus, and bladder. We anticipate that this simple and efficient approach will facilitate the use of mouse models for studying a wide range of epithelia by providing highly enriched populations of diverse p63+ epithelial progenitor cells in quantity.
format	article
author	Daisuke Suzuki Filipa Pinto Makoto Senoo
author_facet	Daisuke Suzuki Filipa Pinto Makoto Senoo
author_sort	Daisuke Suzuki
title	Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
title_short	Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
title_full	Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
title_fullStr	Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
title_full_unstemmed	Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
title_sort	inhibition of tgf-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e45c0d6025d24b75895a7215ab9b5e92
work_keys_str_mv	AT daisukesuzuki inhibitionoftgfbsignalingsupportshighproliferativepotentialofdiversep63mouseepithelialprogenitorcellsinvitro AT filipapinto inhibitionoftgfbsignalingsupportshighproliferativepotentialofdiversep63mouseepithelialprogenitorcellsinvitro AT makotosenoo inhibitionoftgfbsignalingsupportshighproliferativepotentialofdiversep63mouseepithelialprogenitorcellsinvitro
_version_	1718388550280413184

Inhibition of TGF-β signaling supports high proliferative potential of diverse p63+ mouse epithelial progenitor cells in vitro

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