Joakim Lundeberg, PhD; Xiaowei Zhuang, PhD; Imaging: Genomic Innovation and Precision Medicine Conference: April 5 2022

Joakim Lundeberg, PhD (Start of video- minute 36:30)

Professor in Molecular Biotechnology, KTH Royal Institute of Technology Exploring the Spatial and Multimodal Landscape in Tumors

ABSTRACT

The proximal environment of tumors forms an intricate network of various cell-cell interactions, and spatially resolved transcriptomics carries great potential to unravel signaling pathways, which can be screened for new therapeutic targets and provide a fundamental understanding of tumor biology. We have previously reported using spatial transcriptomics methodology in prostate, breast, and squamous cell cancer. Here, a computational deconvolution approach was used to define and characterize tumor-specific expression profiles of multifocal cancer sites together with stromal and immune compartments. This unbiased analysis of the tumor revealed that cancer-associated expression patterns appeared in regions where histological evidence was missing, thus highlighting the potential of unbiased gene expression approaches to capture signals otherwise missed by conventional histopathology. Indeed, defining the transition from benign to malignant tissue by molecular strategies will be fundamental to improving cancer’s early diagnosis. In this presentation, we describe an approach for an unsupervised analysis to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumors and in nearby benign tissue. Our results suggest a model for genomic instability in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms. ________________________________________________________________________________

Xiaowei Zhuang, PhD (Minute 38:24-end of video)

David B. Arnold Professor of Science and Investigator, Howard Hughes Medical Institute, Harvard University

Spatially Resolved Single-Cell Genomics and Cell Atlases of Complex Tissues

ABSTRACT

Inside living organisms, thousands of different genes function collectively to give rise to cellular behavior and tissue function. Understanding the behaviors and functions of cells and tissues thus require imaging at the genome scale, which will advance our understanding in many areas of biology, ranging from gene regulation in cells to the development of cell fate and organization of cell types in complex tissues. We developed a single-cell transcriptome and genome imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH), which allows RNA, DNA, and epigenomic mark imaging at the genome scale. Using this method, we demonstrated simultaneous imaging, localization, and quantification of thousands of genes and genomic loci in individual cells. This approach enabled in situ, spatially resolved transcripto micprofiling, epigenomic profiling, and 3D genome organization mapping in single cells. The ability to perform single-cell gene expression profiling in intact tissues further enabled the identification, spatial mapping, and functional annotation of distinct cell types in intact tissues. In this talk, I will describe the MERFISH technology and its applications, with a focus on mapping the molecular, spatial, and functional organizations of cell types in the brain.