Two awards for the Van Rheenen-lab!

Two researchers from the lab of prof. Jacco van Rheenen received an award this week.  Anoek Zomer received the ESMI Award for excellent PhD thesis and Jessica Morgner received the Young Investigator Award from the Deutsche Gesellschaft für Matrix Biologie.

Anoek Zomer: “Intravital imaging of plasticity during tumor growth and metastasis“

Most tumors consist of a heterogeneous mixture of genetically and epigenetically distinct tumor cells. In addition, tumors display regional differences in the tumor microenvironment comprising non-transformed cell types such as immune cells and non-cellular factors including growth factors and the extracellular matrix. As a consequence of this intra-tumor heterogeneity, individual tumor cells may differ in a variety of features such as the ability to contribute to growth and to metastasize. Complications after metastatic spread are the major cause of cancer-related deaths, but the precise contribution of intra-tumor heterogeneity to this clinical problem is still not fully understood.

To investigate the full complexity of heterogeneous tumors, until recently, most studies relied on the use of relatively large numbers of cells, for example for genome-wide sequencing or proteomics. However, the presence of rare but biologically relevant cells is difficult to resolve from these data, and thus these methods may not completely reveal the full spectrum of heterogeneity. While techniques such as histochemistry or single cell sequencing significantly contributed to a more detailed understanding of intra-tumor heterogeneity on a single cell level, these methods only provide a static view and do not assess the adaptive properties and functional role of individual cells present in living organisms. To study in vivo dynamics of single cells within heterogeneous tumors, in the studies described in this thesis we make use of fluorescent mouse models and intravital microscopy, an imaging technique by which individual cells inside a living organism can be visualized at subcellular resolution. Using these methods I 1) visualized and characterized the growth of breast tumors in living mice, and 2) studied the exchange of biomolecules through extracellular vesicles in living mice.

Source

Jessica Morgner: “Integrin-linked kinase regulates the niche of quiescent epidermal stem cells”

Stem cells reside in specialized niches that are critical for their function. Quiescent hair follicle stem cells (HFSCs) are confined within the bulge niche, but how the molecular composition of the niche regulates stem cell behaviour is poorly understood. Here we show that integrin-linked kinase (ILK) is a key regulator of the bulge extracellular matrix microenvironment, thereby governing the activation and maintenance of HFSCs. ILK mediates deposition of inverse laminin (LN)-332 and LN-511 gradients within the basement membrane (BM) wrapping the hair follicles. The precise BM composition tunes activities of Wnt and transforming growth factor-β pathways and subsequently regulates HFSC activation. Notably, reconstituting an optimal LN microenvironment restores the altered signalling in ILK-deficient cells. Aberrant stem cell activation in ILK-deficient epidermis leads to increased replicative stress, predisposing the tissue to carcinogenesis. Overall, our findings uncover a critical role for the BM niche in regulating stem cell activation and thereby skin homeostasis.

Source