Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.

Autor: Nanba D; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland.; Division of Aging and Regeneration, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Sakabe JI; Duke-NUS Medical School, Singapore City, Singapore.; Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital and A*STAR Skin Research Labs, Singapore City, Singapore., Mosig J; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Brouard M; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Toki F; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland.; Division of Aging and Regeneration, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Shimokawa M; Division of Aging and Regeneration, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Kamiya M; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Braschler T; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland.; Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Azzabi F; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Droz-Georget Lathion S; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Johnsson K; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland., Roy K; Duke-NUS Medical School, Singapore City, Singapore.; Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital and A*STAR Skin Research Labs, Singapore City, Singapore., Schmid CD; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Bureau JB; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Rochat A; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland., Barrandon Y; Laboratory of Stem Cell Dynamics, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Department of Experimental Surgery, Lausanne University Hospital, Lausanne, Switzerland.; Duke-NUS Medical School, Singapore City, Singapore.; Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital and A*STAR Skin Research Labs, Singapore City, Singapore.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Jun 05; Vol. 24 (6), pp. e55439. Date of Electronic Publication: 2023 May 04.
DOI: 10.15252/embr.202255439
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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