دورية أكاديمية
أعرض في EDS

Soft extracellular matrix drives endoplasmic reticulum stress-dependent S quiescence underlying molecular traits of pulmonary basal cells.

التفاصيل البيبلوغرافية
العنوان: Soft extracellular matrix drives endoplasmic reticulum stress-dependent S quiescence underlying molecular traits of pulmonary basal cells.
المؤلفون: Laval PA; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Piecyk M; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Guen PL; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Ilie MD; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Endocrinology Department, 'C.I.Parhon' National Institute of Endocrinology, Bucharest, Romania., Marion A; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Fauvre J; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Coste I; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Renno T; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Aznar N; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Hadji C; Cell&Soft, Grenoble, France., Migdal C; Cell&Soft, Grenoble, France., Duret C; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Bertolino P; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Ferraro-Peyret C; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Plateforme AURAGEN, Lyon, France., Nicolas A; University Grenoble Alpes, CNRS, CEA/LETI Minatec, Grenoble Institute of Technology, Laboratory of Technology of Microelectronics, Grenoble, France., Chaveroux C; Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France. Electronic address: cedric.chaveroux@lyon.unicancer.fr.
المصدر: Acta biomaterialia [Acta Biomater] 2024 Jul 01; Vol. 182, pp. 93-110. Date of Electronic Publication: 2024 May 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 101233144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-7568 (Electronic) Linking ISSN: 17427061 NLM ISO Abbreviation: Acta Biomater Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Kidlington, Oxford, UK : Elsevier, c2004-
مواضيع طبية MeSH: Endoplasmic Reticulum Stress* , Extracellular Matrix*/metabolism, Humans ; Lung/metabolism ; Cell Differentiation ; Hydrogels/chemistry
مستخلص: Cell culture on soft matrix, either in 2D and 3D, preserves the characteristics of progenitors. However, the mechanism by which the mechanical microenvironment determines progenitor phenotype, and its relevance to human biology, remains poorly described. Here we designed multi-well hydrogel plates with a high degree of physico-chemical uniformity to reliably address the molecular mechanism underlying cell state modification driven by physiological stiffness. Cell cycle, differentiation and metabolic activity could be studied in parallel assays, showing that the soft environment promotes an atypical S-phase quiescence and prevents cell drift, while preserving the differentiation capacities of human bronchoepithelial cells. These softness-sensitive responses are associated with calcium leakage from the endoplasmic reticulum (ER) and defects in proteostasis and enhanced basal ER stress. The analysis of available single cell data of the human lung also showed that this non-conventional state coming from the soft extracellular environment is indeed consistent with molecular feature of pulmonary basal cells. Overall, this study demonstrates that mechanical mimicry in 2D culture supports allows to maintain progenitor cells in a state of high physiological relevance for characterizing the molecular events that govern progenitor biology in human tissues. STATEMENT OF SIGNIFICANCE: This study focuses on the molecular mechanism behind the progenitor state induced by a soft environment. Using innovative hydrogel supports mimicking normal human lung stiffness, the data presented demonstrate that lung mechanics prevent drift while preserving the differentiation capabilities of lung epithelial cells. Furthermore, we show that the cells are positioned in a quiescent state in the atypical S phase. Mechanistically, we demonstrate that this quiescence: i) is driven by calcium leakage from the endoplasmic reticulum (ER) and basal activation of the PERK branch of ER stress signalling, and ii) protects cells from lethal ER stress caused by metabolic stress. Finally, we validate using human single-cell data that these molecular features identified on the soft matrix are found in basal lung cells. Our results reveal original and relevant molecular mechanisms orchestrating cell fate in a soft environment and resistance to exogenous stresses, thus providing new fundamental and clinical insights into basal cell biology.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A. Nicolas and C. Migdal are shareholders of the Cell&Soft company.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
فهرسة مساهمة: Keywords: Cell drift and differentiation capability; Physiological ER stress; Resistance to metabolic stress; S-phase quiescence; Stiffness
المشرفين على المادة: 0 (Hydrogels)
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240617 Latest Revision: 20240620
رمز التحديث: 20240620
DOI: 10.1016/j.actbio.2024.05.033
PMID: 38788988
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-7568
DOI:10.1016/j.actbio.2024.05.033