Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium

Abstract Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the...

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Autores principales:	Zixian Zhao, Yujia Wang, Yingchuan Wu, Dandan Li, Ting Zhang, Yu Ma, Xiaoming Teng, Wei Zuo
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	Cervix Stem cells Regeneration Single-cell RNA-seq Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c8a023683c044638875262e5c4d28911
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spelling	oai:doaj.org-article:c8a023683c044638875262e5c4d289112021-11-08T11:15:46ZSingle-cell analysis defines the lineage plasticity of stem cells in cervix epithelium10.1186/s13619-021-00096-22045-9769https://doaj.org/article/c8a023683c044638875262e5c4d289112021-11-01T00:00:00Zhttps://doi.org/10.1186/s13619-021-00096-2https://doaj.org/toc/2045-9769Abstract Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.Zixian ZhaoYujia WangYingchuan WuDandan LiTing ZhangYu MaXiaoming TengWei ZuoSpringerOpenarticleCervixStem cellsRegenerationSingle-cell RNA-seqMedicine (General)R5-920Biology (General)QH301-705.5ENCell Regeneration, Vol 10, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cervix Stem cells Regeneration Single-cell RNA-seq Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Cervix Stem cells Regeneration Single-cell RNA-seq Medicine (General) R5-920 Biology (General) QH301-705.5 Zixian Zhao Yujia Wang Yingchuan Wu Dandan Li Ting Zhang Yu Ma Xiaoming Teng Wei Zuo Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
description	Abstract Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.
format	article
author	Zixian Zhao Yujia Wang Yingchuan Wu Dandan Li Ting Zhang Yu Ma Xiaoming Teng Wei Zuo
author_facet	Zixian Zhao Yujia Wang Yingchuan Wu Dandan Li Ting Zhang Yu Ma Xiaoming Teng Wei Zuo
author_sort	Zixian Zhao
title	Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
title_short	Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
title_full	Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
title_fullStr	Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
title_full_unstemmed	Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
title_sort	single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/c8a023683c044638875262e5c4d28911
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Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium

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