Prof. Dr. Sara Wickström
Regulation of stem cell fate and tissue function through mechanochemical signals from the niche
Cell Biology / Molecular Biology
Cell Mechanics
Stem Cell Biology
Epigenetics
Development
Tissue structures and cell morphologies are adapted to their specialized functions. While executing these specialized functions, tissues and single cells are exposed to and generate tissue-specific mechanical forces such as shear stress, compression, differential tissue rigidity, and strain, to which they respond to by engaging mechanisms of mechanotransduction. These forces function as important signaling ques that are transmitted to the nucleus to alter genetic programs and thus cell behavior. On the other hand, excessive mechanical stresses have the potential to damage cells and tissues.
Control of three-dimensional genome organization and nuclear architecture are critical for precise regulation of gene expression and thus establishment and maintenance of cell identity. These mechanisms are further perturbed in cancer. Our studies show that mechanical force remodels nuclear architecture, chromatin state, and global gene expression patterns to control stem cell differentiation and tissue function, and we now aim to understand the molecular mechanisms and functional significance of these effects in human health and disease. Research in the lab combines mouse genetics and human patient material with scale-bridging technologies from nanoscale atomic force microscopy and next generation sequencing to whole organism live imaging and in silico modeling. The research is highly interdisciplinary and involves collaborations with mathematicians, physicists and clinical oncologists.
Vita
- 2001 M.D., University of Helsinki, Finland
- 2004 Ph.D. (Dr. Med. Sci), University of Helsinki, Finland
- 2004 - 2005 General Practitioner, Viiskulma Health Care Center, Helsinki, Finland
- 2005 - 2010 Postdoctoral Fellow (Fässler lab), MPI for Biochemistry, Martinsried
- 2010 - 2020 Max Planck Research Group Leader, MPI-AGE, Cologne, Germany
- 2018 - 2020 Associate Professor, Helsinki Institute of Life Science, Helsinki, Finland
- 2020 Elected EMBO Member
- 2021- 2022 Professor of Cell and Developmental Biology (Tenured), Faculty of Medicine,
University of Helsinki, Finland - Since 2021 Director, Department of Cell and Tissue Dynamics,
Max Planck Institute for Molecular Biomedicine, Muenster, Germany
Selected references
Koester J, Miroshnikova YA, Ghatak S, Chacón-Martínez CA, Morgner J, Li X, Atanassov I, Koch M, Bloch W, Bartusel M, Niessen CM, Rada-Iglesias A, Wickström SA. (2021) Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters. Nat Cell Biol 7:771-781.
Kim CS, Ding X, Allmeroth K, Biggs, LC, Kolenc OI, L’Hoest N, Chacón-Martínez CA, Edlich-Muth C, Giavalisco P, Quinn KP, Denzel M, Eming SA, Wickström SA. (2020) Glutamine metabolism controls stem cell fate reversibility and long-term maintenance in the hair follicle. Cell Metabolism 32, 629-642.e8
Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, Wickström SA. (2020) Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage Cell 181, 800-817
Miroshnikova YA, Le, HQ, Schneider D, Thalheim T, Rübsam M, Bremicker N, Polleux J, Höppner N, Tarantola M, Wang I, Balland M, Niessen CM, Galle J, Wickström SA (2018) Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification. Nat Cell Biol 20:69-80.
Le HQ, Ghatak S, Yeung CY, Tellkamp F, Günschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström SA. (2016). Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nat Cell Biol. 18, 864-875.