Substrate softness promotes terminal differentiation of human keratinocytes without altering their ability to proliferate back into a rigid environment
| Autor: | Mariana Carrancá, Romain Debret, Dominique Sigaudo-Roussel, Bérengère Fromy, Choua Ya, Philippe Faure |
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| Přispěvatelé: | Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
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Keratinocytes Polyacrylamide Hydrogel [SDV]Life Sciences [q-bio] Foreskin Primary Cell Culture Cell Proliferation Mechanical properties Dermatology Matrix (biology) Transcriptome 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine medicine Humans RNA-Seq Receptor Cells Cultured Cell Proliferation Transcriptome profiling Chemistry Infant Newborn Cell Differentiation General Medicine Cell biology medicine.anatomical_structure Cellular Microenvironment 030220 oncology & carcinogenesis Differentiation Self-healing hydrogels Keratinocyte Reprogramming |
| Zdroj: | Archives of Dermatological Research Archives of Dermatological Research, Springer Verlag, 2019, 311 (10), pp.741-751. ⟨10.1007/s00403-019-01962-5⟩ |
| ISSN: | 0340-3696 1432-069X |
| Popis: | International audience; Substrate stiffness is a key regulator of cell behavior. To investigate how mechanical properties of cell microenvironment affect the human keratinocyte, primary cells were seeded on polyacrylamide hydrogels of different compliances (soft: 4 kPa, medium: 14 kPa, rigid: 45 kPa) in comparison with glass coverslip (> GPa). Keratinocyte spreading and proliferation were strongly decreased on the softest hydrogel, while no significant difference was observed between medium, rigid hydrogels and glass coverslip, and cells' viability was comparable in all conditions after 72 h. We then performed a RNA-seq to compare the transcriptomes from keratinocytes cultured for 72 h on the softest hydrogel or on coverslips. The cells on the soft hydrogel showed a strong increase in the expression of late differentiation marker genes from the epidermal differentiation complex (1q21) and the antioxidant machinery. In parallel, these cells displayed a significant loss of expression of the matrix receptors (integrin α6 and β1) and the EGF receptor. However, when these cells were replated on a plastic culture plate (> GPa), they were able to re-engage the proliferation machinery with a strong colony-formation efficiency. Overall, using low-calcium differentiation monolayers at confluence, the lesser the rigidity, the stronger the markers of late differentiation are expressed, while the inverse is observed regarding the markers of early differentiation. In conclusion, below a certain rigidity, human keratinocytes undergo genome reprogramming indicating terminal differentiation that can switch back to proliferation in contact with a stiffer environment. |
| Databáze: | OpenAIRE |
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