Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.
Details
Serval ID
serval:BIB_4FEF24645C11
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.
Journal
EMBO reports
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
05/06/2023
Peer-reviewed
Oui
Volume
24
Number
6
Pages
e55439
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Adult autologous human epidermal stem cells can be extensively expanded ex vivo for cell and gene therapy. Identifying the mechanisms involved in stem cell maintenance and defining culture conditions to maintain stemness is critical, because an inadequate environment can result in the rapid conversion of stem cells into progenitors/transient amplifying cells (clonal conversion), with deleterious consequences on the quality of the transplants and their ability to engraft. Here, we demonstrate that cultured human epidermal stem cells respond to a small drop in temperature through thermoTRP channels via mTOR signaling. Exposure of cells to rapamycin or a small drop in temperature induces the nuclear translocation of mTOR with an impact on gene expression. We also demonstrate by single-cell analysis that long-term inhibition of mTORC1 reduces clonal conversion and favors the maintenance of stemness. Taken together, our results demonstrate that human keratinocyte stem cells can adapt to environmental changes (e.g., small variations in temperature) through mTOR signaling and constant inhibition of mTORC1 favors stem cell maintenance, a finding of high importance for regenerative medicine applications.
Keywords
Adult, Humans, Temperature, Keratinocytes/metabolism, TOR Serine-Threonine Kinases/metabolism, Stem Cells/metabolism, Mechanistic Target of Rapamycin Complex 1, TRP channels, keratinocyte stem cells, mTOR, microenvironment, temperature
Pubmed
Web of science
Open Access
Yes
Create date
08/05/2023 12:38
Last modification date
22/01/2024 14:24