Cargando…
Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium
Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 p...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938507/ https://www.ncbi.nlm.nih.gov/pubmed/35314700 http://dx.doi.org/10.1038/s41467-022-29165-z |
_version_ | 1784672567277125632 |
---|---|
author | Higa, Tsunaki Okita, Yasutaka Matsumoto, Akinobu Nakayama, Shogo Oka, Takeru Sugahara, Osamu Koga, Daisuke Takeishi, Shoichiro Nakatsumi, Hirokazu Hosen, Naoki Robine, Sylvie Taketo, Makoto M. Sato, Toshiro Nakayama, Keiichi I. |
author_facet | Higa, Tsunaki Okita, Yasutaka Matsumoto, Akinobu Nakayama, Shogo Oka, Takeru Sugahara, Osamu Koga, Daisuke Takeishi, Shoichiro Nakatsumi, Hirokazu Hosen, Naoki Robine, Sylvie Taketo, Makoto M. Sato, Toshiro Nakayama, Keiichi I. |
author_sort | Higa, Tsunaki |
collection | PubMed |
description | Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 position of intestinal crypts. Lineage tracing reveals that the p57(+) cells serve as enteroendocrine/tuft cell precursors under normal conditions but dedifferentiate and act as facultative stem cells to support regeneration after injury. Single-cell transcriptomics analysis shows that the p57(+) cells undergo a dynamic reprogramming process after injury that is characterized by fetal-like conversion and metaplasia-like transformation. Population-level analysis also detects such spatiotemporal reprogramming widely in other differentiated cell types. In intestinal adenoma, p57(+) cells manifest homeostatic stem cell activity, in the context of constitutively activated spatiotemporal reprogramming. Our results highlight a pronounced plasticity of the intestinal epithelium that supports maintenance of tissue integrity in normal and neoplastic contexts. |
format | Online Article Text |
id | pubmed-8938507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89385072022-04-08 Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium Higa, Tsunaki Okita, Yasutaka Matsumoto, Akinobu Nakayama, Shogo Oka, Takeru Sugahara, Osamu Koga, Daisuke Takeishi, Shoichiro Nakatsumi, Hirokazu Hosen, Naoki Robine, Sylvie Taketo, Makoto M. Sato, Toshiro Nakayama, Keiichi I. Nat Commun Article Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 position of intestinal crypts. Lineage tracing reveals that the p57(+) cells serve as enteroendocrine/tuft cell precursors under normal conditions but dedifferentiate and act as facultative stem cells to support regeneration after injury. Single-cell transcriptomics analysis shows that the p57(+) cells undergo a dynamic reprogramming process after injury that is characterized by fetal-like conversion and metaplasia-like transformation. Population-level analysis also detects such spatiotemporal reprogramming widely in other differentiated cell types. In intestinal adenoma, p57(+) cells manifest homeostatic stem cell activity, in the context of constitutively activated spatiotemporal reprogramming. Our results highlight a pronounced plasticity of the intestinal epithelium that supports maintenance of tissue integrity in normal and neoplastic contexts. Nature Publishing Group UK 2022-03-21 /pmc/articles/PMC8938507/ /pubmed/35314700 http://dx.doi.org/10.1038/s41467-022-29165-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Higa, Tsunaki Okita, Yasutaka Matsumoto, Akinobu Nakayama, Shogo Oka, Takeru Sugahara, Osamu Koga, Daisuke Takeishi, Shoichiro Nakatsumi, Hirokazu Hosen, Naoki Robine, Sylvie Taketo, Makoto M. Sato, Toshiro Nakayama, Keiichi I. Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title | Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title_full | Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title_fullStr | Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title_full_unstemmed | Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title_short | Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
title_sort | spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938507/ https://www.ncbi.nlm.nih.gov/pubmed/35314700 http://dx.doi.org/10.1038/s41467-022-29165-z |
work_keys_str_mv | AT higatsunaki spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT okitayasutaka spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT matsumotoakinobu spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT nakayamashogo spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT okatakeru spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT sugaharaosamu spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT kogadaisuke spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT takeishishoichiro spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT nakatsumihirokazu spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT hosennaoki spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT robinesylvie spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT taketomakotom spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT satotoshiro spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium AT nakayamakeiichii spatiotemporalreprogrammingofdifferentiatedcellsunderliesregenerationandneoplasiaintheintestinalepithelium |