@article{632a3968eb064be88dbb061fb29d0d2c,
title = "Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium",
abstract = "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.",
author = "Tsunaki Higa and Yasutaka Okita and Akinobu Matsumoto and Shogo Nakayama and Takeru Oka and Osamu Sugahara and Daisuke Koga and Shoichiro Takeishi and Hirokazu Nakatsumi and Naoki Hosen and Sylvie Robine and Taketo, {Makoto M.} and Toshiro Sato and Nakayama, {Keiichi I.}",
note = "Funding Information: We thank F. de Sauvage (Genentech Inc.) for providing Lgr5-DTR-EGFP transgenic mice, Y. Ohkawa (Medical Institute of Bioregulation, Kyushu University) for discussion on scRNA-seq experiments, M. Ikawa (Research Institute for Microbial Diseases, Osaka, Japan) for discussion on generation of knock-in mice, as well as A. Niihara, H. Takayoshi, M. Tanaka, and K. Nagatoshi for technical assistance. This work was supported in part by KAKENHI grants from Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science, and Technology of Japan to K.I.N. (JP18H05215) and to T.H. (JP19K16716) as well as by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) of the Japan Agency for Medical Research and Development (AMED) to K.I.N. (JP21cm0106105). Funding Information: We thank F. de Sauvage (Genentech Inc.) for providing Lgr5-DTR-EGFP transgenic mice, Y. Ohkawa (Medical Institute of Bioregulation, Kyushu University) for discussion on scRNA-seq experiments, M. Ikawa (Research Institute for Microbial Diseases, Osaka, Japan) for discussion on generation of knock-in mice, as well as A. Niihara, H. Takayoshi, M. Tanaka, and K. Nagatoshi for technical assistance. This work was supported in part by KAKENHI grants from Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science, and Technology of Japan to K.I.N. (JP18H05215) and to T.H. (JP19K16716) as well as by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) of the Japan Agency for Medical Research and Development (AMED) to K.I.N. (JP21cm0106105). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-29165-z",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}