Micro-Topographies Induce Epigenetic Reprogramming and Quiescence in Human Mesenchymal Stem Cells

Steven Vermeulen, Bart Van Puyvelde, Laura Bengtsson del Barrio, Ruben Almey, Bernard K. van der Veer, Dieter Deforce, Maarten Dhaenens, Jan de Boer (Corresponding author)

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Abstract

Biomaterials can control cell and nuclear morphology. Since the shape of the nucleus influences chromatin architecture, gene expression and cell identity, surface topography can control cell phenotype. This study provides fundamental insights into how surface topography influences nuclear morphology, histone modifications, and expression of histone-associated proteins through advanced histone mass spectrometry and microarray analysis. The authors find that nuclear confinement is associated with a loss of histone acetylation and nucleoli abundance, while pathway analysis reveals a substantial reduction in gene expression associated with chromosome organization. In light of previous observations where the authors found a decrease in proliferation and metabolism induced by micro-topographies, they connect these findings with a quiescent phenotype in mesenchymal stem cells, as further shown by a reduction of ribosomal proteins and the maintenance of multipotency on micro-topographies after long-term culture conditions. Also, this influence of micro-topographies on nuclear morphology and proliferation is reversible, as shown by a return of proliferation when re-cultured on a flat surface. The findings provide novel insights into how biophysical signaling influences the epigenetic landscape and subsequent cellular phenotype.

Original languageEnglish
Article number2203880
Number of pages15
JournalAdvanced Science
Volume10
Issue number1
DOIs
Publication statusPublished - 4 Jan 2023

Bibliographical note

Funding Information:
S.V., L.B.B., and B.K.V. acknowledge the financial support of the Dutch province of Limburg. S.V. is supported by the European Union's Horizon 2020 Programme (H2020‐MSCA‐ITN‐2015; Grant agreement 676338). B.K.V., B.V.P., and M.D. were funded by grants from the Research Foundation Flanders (FWO, grant numbers: 11E7920N to B.K.V., 11B4518N to B.V.P., and 12E9716N to M.D.). R.A. was funded by a grant from the Special Research Fund Ghent University (BOF, grant number: BOFDOC2021002202).

Keywords

  • biomaterials
  • epigenetics
  • mechanobiology
  • mesenchymal stem cells
  • nucleus

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