Global Faculty University of Cologne, Director MPI for Moledular Biomedicine
The skin is a self-renewing organ constantly exposed to environmental influences, such as injury, UV rays and toxic substances. To maintain a functional tissue, stem cells differentiate to replace cells that are lost through damage or normal turnover. The group led by Prof. Dr. Wickström works to identify mechanisms that regulate stem cell differentiation. The central focus is on characterizing fundamental mechanisms of this process and in understanding why skin loses regenerative power as we age, and how stem cell dysregulation promotes the genesis of skin cancer.
Our research: Due to its self-renewing nature skin is optimally suited for stem cell research. Stem cells play key roles in replenishing tissues with differentiated cells that are lost during homeostatic renewal or during injury. Furthermore, stem cell dysfunction leads to tissue degeneration, aging and cancer. Therefore, understanding how stem cells function is critical for understanding how these diseases develop and how they might be treated. The research group led by Prof. Dr. Sara Wickström focuses on understanding these processes in detail.
Our successes: Prof. Dr. Wickström and her group have shown how the local microenvironment of the stem cells affects their behavior, and its importance for maintaining the stem cell population during aging and for protecting the tissue from cancer. The group has successfully decoded the molecular basis for this process. The scientists are collaborating on translational projects on skin cancer by studying human tumor samples. In another project the group discovered a mechanism by which cells deposit connective tissue. This mechanism is important also in fibrosis, a disease where connective tissue is produced in excess. Therefore this mechanism could be exploited to treat these patients.
Our goals: In future, the research group will focus on more detailed understanding of stem cell regulation in the skin. In addition the group hopes to be able to test some approaches
in clinical trials, in particular for treating fibrosis. For this Prof. Dr. Wickström and her team work together with Prof. Krieg from the Department of Dermatology, who heads the national network for systemic sclerosis, a severe form of fibrotic disease.
Our methods/techniques: The scientists apply a combination of mouse genetics and cell biology in the following three main areas: (1) mechanisms of force generation in matrix remodeling and tissue repair, (2) role of cell-matrix interactions in stem cell fate, carcinogenesis and aging, and (3) mechanotransduction in skin homeostasis and aging.
Figure 1: Immunofluorescence staining of mouse hair follicle stem cells. Stem cells of the skin and hair follicles (red) are critical for the maintenance and regeneration of the tissue. An important question is how stem cells interact with their environment and how these interactions affect stem cell function and therefore impact tissue regeneration and ageing.
Figure 2: Cells sense their environment by generating forces on the surrounding extracellular matrix.
(A) Immunofluorescence staining of the actin cytoskeleton (green) and cell adhesion complexes (red).
(B) A heat-scale map of forces generated by a skin fibroblast on the extracellular matrix. Gene deletion of the adhesion complex component Integrin-linked kinase (ILK -/-) impairs the ability of cells to organize their cytoskeleton and to generate forces (C).
Figure 3: Engineering micropatterned surfaces to study stem behavior. To understand how cell density, size and shape affects stem cell behavior, special micropatterned adhesion surfaces can be engineered. The surfaces restrict the adhesive area of the cells, thereby forcing them into a specific shape or density, in this case 30 µm-sized circles. The actin cytoskeleton has been labeled red and nuclei in blue.