In this episode of the Epigenetics Podcast, we caught up with Sara Wickström, Director at the Max Planck Institute for Molecular Biomedicine in Münster, to talk about her work on the effect of mechanotransduction on chromatin structure and transcription in stem cells.
Sara Wickström and her team focus on the stem cell niche and how that niche affects stem cell function. In order to study the native niche and to even be able to manipulate it, the Wickström Lab was able to develop a ex vivo culture system, allowing systematic identification of factors driving stem cell dynamics and plasticity.
Stem cells in the stem cell niche are exposed to external stimuli such as physical forces which control their growth, fate and self renewal. Recent work in the Wickström lab showed how mechanical signals influence transcriptional regulation, chromatin organization, and nuclear architecture and how this affects aging or lineage commitment. In this Episode we also discuss how chromatin can act as a sensor of mechanical signals taking advantage of the different physical properties of eu- and heterochromatin.
Le, H. Q., Ghatak, S., Yeung, C. Y., Tellkamp, F., Günschmann, C., Dieterich, C., Yeroslaviz, A., Habermann, B., Pombo, A., Niessen, C. M., & Wickström, S. A. (2016). Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nature cell biology, 18(8), 864–875. https://doi.org/10.1038/ncb3387
Nava, M. M., Miroshnikova, Y. A., Biggs, L. C., Whitefield, D. B., Metge, F., Boucas, J., Vihinen, H., Jokitalo, E., Li, X., García Arcos, J. M., Hoffmann, B., Merkel, R., Niessen, C. M., Dahl, K. N., & Wickström, S. A. (2020). Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell, 181(4), 800–817.e22. https://doi.org/10.1016/j.cell.2020.03.052
Koester, J., Miroshnikova, Y. A., Ghatak, S., Chacón-Martínez, C. A., Morgner, J., Li, X., Atanassov, I., Altmüller, J., Birk, D. E., Koch, M., Bloch, W., Bartusel, M., Niessen, C. M., Rada-Iglesias, A., & Wickström, S. A. (2021). Niche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility. Nature cell biology, 23(7), 771–781. https://doi.org/10.1038/s41556-021-00705-x
Maki, K., Nava, M. M., Villeneuve, C., Chang, M., Furukawa, K. S., Ushida, T., & Wickström, S. A. (2021). Hydrostatic pressure prevents chondrocyte differentiation through heterochromatin remodeling. Journal of cell science, 134(2), jcs247643. https://doi.org/10.1242/jcs.247643