Unraveling Tumor Microenvironment Heterogeneity in Advanced Prostrate Cancer
Abstract
Prostate cancer (PCa) is one of the leading causes of cancer-related death in men worldwide, but efforts to delineate patients with advanced disease has been marred by widespread inter- and intra-tumor heterogeneity. While a significant fraction of our work was stalled by the ongoing pandemic, we were still able to quantify tissue composition and heterogeneity by single-cell analysis. We found that all cells of the human prostate are present in the mouse prostate, but the mouse prostate bears hitherto known exceptional diversity of cell types, including multiple luminal epithelial cell sub-types. We find that gene signatures of neuroendocrine cells (NE) of the mouse prostate resembles that of NE cells of the mouse lung and NE prostate cancers (NEPCs). As single-cell RNA sequencing requires large amounts (1-10 g) of fresh tissues that are often not clinically accessible we developed a novel pipeline for single-nucleus RNA sequencing and single-nucleus ATAC sequencing from small amounts (0.1-1g) of archived (frozen) tissues from autopsies. We have now generated the cell atlas of benign prostates, localized prostate cancer of distinct grades, metastatic PCa from four different sites and NEPCs. We are currently correlating clinical information with our single cell data for prostate tumor stratification.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1122432
Entities
People
- Sethuramasundaram Pitchiaya
Organizations
- University of Michigan