Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures

Lung epithelial progenitors differentiate into alveolar type 1 (AT1) and type 2 (AT2) cells. These cells form the air-blood interface and secrete surfactant, respectively, and are essential for lung maturation and function. Current protocols to derive and culture alveolar cells do not faithfully rec...

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Autores principales:	Konstantinos Gkatzis, Paolo Panza, Sofia Peruzzo, Didier YR Stainier
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	organoids lung alveolus cell differentiation lung development tip progenitor alveolar epithelial cell Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4e6ea6ee77b446c1ba6c16c0a41d7f5c
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spelling	oai:doaj.org-article:4e6ea6ee77b446c1ba6c16c0a41d7f5c2021-11-15T06:44:21ZDifferentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures10.7554/eLife.658112050-084Xe65811https://doaj.org/article/4e6ea6ee77b446c1ba6c16c0a41d7f5c2021-09-01T00:00:00Zhttps://elifesciences.org/articles/65811https://doaj.org/toc/2050-084XLung epithelial progenitors differentiate into alveolar type 1 (AT1) and type 2 (AT2) cells. These cells form the air-blood interface and secrete surfactant, respectively, and are essential for lung maturation and function. Current protocols to derive and culture alveolar cells do not faithfully recapitulate the architecture of the distal lung, which influences cell fate patterns in vivo. Here, we report serum-free conditions that allow for growth and differentiation of mouse distal lung epithelial progenitors. We find that Collagen I promotes the differentiation of flattened, polarized AT1 cells. Using these organoids, we performed a chemical screen to investigate WNT signaling in epithelial differentiation. We identify an association between Casein Kinase activity and maintenance of an AT2 expression signature; Casein Kinase inhibition leads to an increase in AT1/progenitor cell ratio. These organoids provide a simplified model of alveolar differentiation and constitute a scalable screening platform to identify and analyze cell differentiation mechanisms.Konstantinos GkatzisPaolo PanzaSofia PeruzzoDidier YR StainiereLife Sciences Publications Ltdarticleorganoidslung alveoluscell differentiationlung developmenttip progenitoralveolar epithelial cellMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	organoids lung alveolus cell differentiation lung development tip progenitor alveolar epithelial cell Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	organoids lung alveolus cell differentiation lung development tip progenitor alveolar epithelial cell Medicine R Science Q Biology (General) QH301-705.5 Konstantinos Gkatzis Paolo Panza Sofia Peruzzo Didier YR Stainier Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
description	Lung epithelial progenitors differentiate into alveolar type 1 (AT1) and type 2 (AT2) cells. These cells form the air-blood interface and secrete surfactant, respectively, and are essential for lung maturation and function. Current protocols to derive and culture alveolar cells do not faithfully recapitulate the architecture of the distal lung, which influences cell fate patterns in vivo. Here, we report serum-free conditions that allow for growth and differentiation of mouse distal lung epithelial progenitors. We find that Collagen I promotes the differentiation of flattened, polarized AT1 cells. Using these organoids, we performed a chemical screen to investigate WNT signaling in epithelial differentiation. We identify an association between Casein Kinase activity and maintenance of an AT2 expression signature; Casein Kinase inhibition leads to an increase in AT1/progenitor cell ratio. These organoids provide a simplified model of alveolar differentiation and constitute a scalable screening platform to identify and analyze cell differentiation mechanisms.
format	article
author	Konstantinos Gkatzis Paolo Panza Sofia Peruzzo Didier YR Stainier
author_facet	Konstantinos Gkatzis Paolo Panza Sofia Peruzzo Didier YR Stainier
author_sort	Konstantinos Gkatzis
title	Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
title_short	Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
title_full	Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
title_fullStr	Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
title_full_unstemmed	Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
title_sort	differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/4e6ea6ee77b446c1ba6c16c0a41d7f5c
work_keys_str_mv	AT konstantinosgkatzis differentiationofmousefetallungalveolarprogenitorsinserumfreeorganotypiccultures AT paolopanza differentiationofmousefetallungalveolarprogenitorsinserumfreeorganotypiccultures AT sofiaperuzzo differentiationofmousefetallungalveolarprogenitorsinserumfreeorganotypiccultures AT didieryrstainier differentiationofmousefetallungalveolarprogenitorsinserumfreeorganotypiccultures
_version_	1718428551325155328

Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures

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