New Spatial Biology insights for disease and pathology
Chairs: Anja Hauser and Bernd Bodenmiller
Thursday, 12.12.2024, 4:15 pm
Keynote Speaker: Bernd Bodenmiller
Affiliation: University of Zurich /ETH Zurich, Zurich, Switzerland
Highly multiplexed imaging of tissues with subcellular resolution by imaging mass cytometry
Cancer is a tissue disease where heterogeneous tumor cells, stromal cells and immune cells form a dynamic ecosystem that evolves to support tumor expansion and ultimately tumor spread. The complexity of this system is the main obstacle to treat cancer. The study of the tumor ecosystem and its cell-to-cell communications is thus essential to enable an understanding of tumor biology, to define new biomarkers, and to identify new therapeutic routs and targets. To understand the workings of the tumor ecosystem, highly multiplexed image information of tumor tissues is essential. Such multiplexed images will reveal which cell types are present in a tumor, their functional states, and how they interact together. Our analysis reveals surprising level of inter and intra-tumor heterogeneity.
Biosketch
Bernd Bodenmiller is a quantitative biologist who develops novel experimental and computational approaches for the quantitative analysis of tumor ecosystems to improve our understanding of the mechanisms of tumor development for the benefit of patients. He is the founding director of the Department of Quantitative Biomedicine (DQBM) at the University of Zurich, which fosters research and education at the interface of biomedical research, biotechnology, and computational biology to guide development of next-generation precision medicine. Prof. Bodenmiller obtained his PhD in the group of Ruedi Aebersold at ETH Zürich. For his postdoctoral training, he joined the laboratory of Garry P. Nolan at Stanford University. In 2012, he became a group leader and in 2013 an SNF/ERC assistant professor at the University of Zürich. In 2019, he was tenured and became the founding director of the DQBM. In October 2020 Prof. Bodenmiller has been appointed as Dual Professor for Quantitative Biomedicine at the UZH and at ETH Zurich. His group pioneered the development of imaging mass cytometry, an approach that enables simultaneously imaging of over 40 proteins and transcripts in tumor tissues (Nat. Methods, 2014; Cell Systems, 2017; Nature 2020) and the histoCAT software toolbox (Nat. Methods, 2017). His groups applies these methods to unravel how cells in the tumor ecosystem drive cancer development to identify mechanisms that might be exploited for therapeutic targeting (Nat. Biotechnology, 2017, Cell, 2017; Cell, 2019).
Short talk by Maria Puschhof
Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany
Molecular drivers of low- to high-grade transition in IDH-mutant glioma
Gliomas are the most common type of brain tumors in adults and the prognosis for patients strongly varies with the subtype and clinical grade. While 5-year survival can be as high as 80% for patients with low-grade tumors, it drops to under 5% for high-grade gliomas. While some gliomas are always highly aggressive (e.g. glioblastoma), IDH-mutant astrocytoma tumors are able to transition from low- to high-grade state. Thus, there is an urgent need to better understand the molecular drivers of this transformation to ultimately develop counteracting therapeutic approaches.
To this end, we have performed in-depth multi-modal profiling of whole astrocytoma tumors from 6 patients combining single nuclei multi-omics and spatial transcriptomics. Applying the Visium CytAssist platform to tissue sections from 69 tissue blocks, we were able to obtain both detailed pathology annotations as well as spatial transcriptomic data for each tissue slice, enabling the identification of transforming (high-grade) regions next to low-grade tumor tissue at the resolution of sequencing spots. Differential gene expression and functional analysis of biological activities was performed using decoupler, a framework to infer biological activities with the aid of prior knowledge database Omnipath. Across donors, low grade regions were enriched for axon ensheathment and the related processes of myelin assembly and oligodendrocyte development. Conversely, tumor cells residing in high grade regions exhibit enhanced cross-talk towards the microenvironment, both through cytokines and voltage-gated channels. Furthermore, high grade lesions were enriched for various biological processes related to neural development, suggesting distinct developmental programs associated with these areas. These observations were consistent with cell type deconvolution of spatial data via cell2location that further characterized cellular niches associated with low versus high grades. Taken together, we present the first spatial characterization of glioma grade transformation and identify candidate cellular and molecular targets for therapeutic intervention.
Short talk by Gesa Krueger
Institute of Immunology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Isle Riems, Germany
Modeling immune responses of cattle to mycobacteria using magnetic bioprinted granulomas
Tuberculosis (TB) remains a threat for human and livestock health. Mycobacteria causing TB are host-adapted pathogens which occasionally spillover to other species. Mycobacterium bovis causes bovine TB, a well-known zoonosis. A hallmark of TB in all hosts are multicellular tissue lesions termed granulomas. Using bovine leukocytes and nanotechnologies we developed a three-dimensional, multicellular granuloma model which we designated in vitro granuloma-like structure (IVGLS). We generated stable IVGLS resembling TB granulomas at innate, made of macrophages, or adaptive stages, containing also lymphocytes. Evaluation of IVGLS by confocal high-content imaging, accessing single-cell data on both image and statistical level, revealed progression of macrophages towards foamy phenotypes and increased apoptotic cell death over time. IVGLS, unlike conventional macrophage monolayers, were permissive for mycobacterial replication and released abundant phagocyte chemoattractants and Th1 cytokines. Magnetic bioprinted bovine granulomas facilitate studying immune responses to mycobacteria in a three-dimensional manner, including spatial mapping. Deciphering protective immune responses within IVGLS could contribute to vaccine development for cattle, whereas unveiling resistance mechanisms may help devise novel interventions for human TB.
