2026-04-29T07:24:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/176702024-11-29T13:35:30Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Chaves-Pérez, Almudena
author
Santos-de-Frutos, Karla
author
de la Rosa, Sergio
author
Herranz-Montoya, Irene
author
Perna, Cristian
author
Djouder, Nabil
funder
Ministerio de Ciencia e Innovación (España)
funder
European Union (EU)
2024-02-08T21:15:19Z
2024-02-08T21:15:19Z
2022-11-07
J Exp Med . 2022;219(11):e20212405.
http://hdl.handle.net/20.500.12105/17670
36098959
10.1084/jem.20212405
1540-9538
The Journal of experimental medicine
Intestinal epithelium regenerates rapidly through proliferation of intestinal stem cells (ISCs), orchestrated by potent mitogens secreted within the crypt niche. However, mechanisms regulating these mitogenic factors remain largely unknown. Here, we demonstrate that transit-amplifying (TA) cells, marked by unconventional prefoldin RPB5 interactor (URI), control R-spondin production to guide ISC proliferation. Genetic intestinal URI ablation in mice injures TA cells, reducing their survival capacity, leading to an inflamed tissue and subsequently decreasing R-spondin levels, thereby causing ISC quiescence and disruption of intestinal structure. R-spondin supplementation or restoration of R-spondin levels via cell death inhibition by c-MYC elimination or the suppression of inflammation reinstates ISC proliferation in URI-depleted mice. However, selective c-MYC and p53 suppression are required to fully restore TA cell survival and differentiation capacity and preserve complete intestinal architecture. Our data reveal an unexpected role of TA cells, which represent a signaling platform instrumental for controlling inflammatory cues and R-spondin production, essential for maintaining ISC proliferation and tissue regeneration.
eng
Transit-amplifying cells control R-spondins in the mouse crypt to modulate intestinal stem cell proliferation.
journal article
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URL
https://repisalud.isciii.es/bitstreams/d5830587-8163-440f-a753-cbed93de7b65/download
File
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d4226e48d2060287312aca85e660a077
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application/pdf
Transit-amplifying cells control_2022.pdf
URL
https://repisalud.isciii.es/bitstreams/a88e568b-7aeb-46aa-acb0-77a809437b0d/download
File
MD5
4bba0881b3fb8fa877d8e7724c1518bc
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text/plain
Transit-amplifying cells control_2022.pdf.txt