TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds

Abstract The use of decellularized whole-organ scaffolds for bioengineering of organs is a promising avenue to circumvent the shortage of donor organs for transplantation. However, recellularization of acellular scaffolds from multicellular organs like the lung with a variety of different cell types...

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Autores principales:	Claudia Bilodeau, Sharareh Shojaie, Olivia Goltsis, Jinxia Wang, Daochun Luo, Cameron Ackerley, Ian M Rogers, Brian Cox, Martin Post
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/8588797879864052b1564c0cf5b704ba
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spelling	oai:doaj.org-article:8588797879864052b1564c0cf5b704ba2021-12-02T13:28:25ZTP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds10.1038/s41536-021-00124-42057-3995https://doaj.org/article/8588797879864052b1564c0cf5b704ba2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00124-4https://doaj.org/toc/2057-3995Abstract The use of decellularized whole-organ scaffolds for bioengineering of organs is a promising avenue to circumvent the shortage of donor organs for transplantation. However, recellularization of acellular scaffolds from multicellular organs like the lung with a variety of different cell types remains a challenge. Multipotent cells could be an ideal cell source for recellularization. Here we investigated the hierarchical differentiation process of multipotent ES-derived endoderm cells into proximal airway epithelial cells on acellular lung scaffolds. The first cells to emerge on the scaffolds were TP63+ cells, followed by TP63+/KRT5+ basal cells, and finally multi-ciliated and secretory airway epithelial cells. TP63+/KRT5+ basal cells on the scaffolds simultaneously expressed KRT14, like basal cells involved in airway repair after injury. Removal of TP63 by CRISPR/Cas9 in the ES cells halted basal and airway cell differentiation on the scaffolds. These findings suggest that differentiation of ES-derived endoderm cells into airway cells on decellularized lung scaffolds proceeds via TP63+ basal cell progenitors and tracks a regenerative repair pathway. Understanding the process of differentiation is key for choosing the cell source for repopulation of a decellularized organ scaffold. Our data support the use of airway basal cells for repopulating the airway side of an acellular lung scaffold.Claudia BilodeauSharareh ShojaieOlivia GoltsisJinxia WangDaochun LuoCameron AckerleyIan M RogersBrian CoxMartin PostNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Claudia Bilodeau Sharareh Shojaie Olivia Goltsis Jinxia Wang Daochun Luo Cameron Ackerley Ian M Rogers Brian Cox Martin Post TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
description	Abstract The use of decellularized whole-organ scaffolds for bioengineering of organs is a promising avenue to circumvent the shortage of donor organs for transplantation. However, recellularization of acellular scaffolds from multicellular organs like the lung with a variety of different cell types remains a challenge. Multipotent cells could be an ideal cell source for recellularization. Here we investigated the hierarchical differentiation process of multipotent ES-derived endoderm cells into proximal airway epithelial cells on acellular lung scaffolds. The first cells to emerge on the scaffolds were TP63+ cells, followed by TP63+/KRT5+ basal cells, and finally multi-ciliated and secretory airway epithelial cells. TP63+/KRT5+ basal cells on the scaffolds simultaneously expressed KRT14, like basal cells involved in airway repair after injury. Removal of TP63 by CRISPR/Cas9 in the ES cells halted basal and airway cell differentiation on the scaffolds. These findings suggest that differentiation of ES-derived endoderm cells into airway cells on decellularized lung scaffolds proceeds via TP63+ basal cell progenitors and tracks a regenerative repair pathway. Understanding the process of differentiation is key for choosing the cell source for repopulation of a decellularized organ scaffold. Our data support the use of airway basal cells for repopulating the airway side of an acellular lung scaffold.
format	article
author	Claudia Bilodeau Sharareh Shojaie Olivia Goltsis Jinxia Wang Daochun Luo Cameron Ackerley Ian M Rogers Brian Cox Martin Post
author_facet	Claudia Bilodeau Sharareh Shojaie Olivia Goltsis Jinxia Wang Daochun Luo Cameron Ackerley Ian M Rogers Brian Cox Martin Post
author_sort	Claudia Bilodeau
title	TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
title_short	TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
title_full	TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
title_fullStr	TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
title_full_unstemmed	TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
title_sort	tp63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8588797879864052b1564c0cf5b704ba
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_version_	1718392985995968512

TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds

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