Abstract 5702: A spatially resolved single cell atlas of the human breast

The human breast consists of lobules connected to an intricate network of ducts that are surrounded by fatty tissues, designed to produce and transport milk to nourish offspring. Histopathology has identified 10 major cell types based on morphological features but have provided limited information on cell states - the transcriptional programs of cell types that reflect different biological functions. In this study we have generated an unbiased ‘cell atlas' of the normal human breast to define the cell types and cell states using single cell RNA sequencing and spatial transcriptomics methods. We performed 3' microdroplet based single cell and nuclei RNA sequencing of 248,687 stromal cells and 89,301 nuclei from 24 women with pathologically normal breast tissues that were collected from mastectomies and reduction mammoplasties. Unbiased expression analysis identified four major cell types: adipocytes, epithelial cells (luminal and basal), fibroblasts and endothelial cells and defined their transcriptional programs. Additionally, 8 minor cell types were identified in the breast, including macrophages, T-cells, natural killer cells, mast cells, pericytes, apocrine cells, neurons and smooth muscle cells. Our data revealed hundreds of novel markers of these cell types and defined their transcriptional programs and cell states. Most cell types had multiple transcriptional programs including luminal epithelial cells (hormone receptor positive and secretory), basal epithelial cells (myoepithelial or basal), endothelial cells (E1, E2, E3), myeloid cells, T-cells and fibroblasts (F1-F4) and provided insight into developmental lineages. We further delineated the spatial organization of these cell types and cell states within the tissue architecture using spatial transcriptomics assay. The breast cell atlas data provides an invaluable normal reference for the research community to understand how normal cell types are reprogrammed in diseases such as breast cancer. Citation Format: Tapsi Kumar, Quy Nguyen, Kevin Nee, Shanshan Bai, Min Hu, Emi Sei, Anita Wood, Jie Wiley, Hui Chen, Alejandro Contreras, Mediget Teshome, Ken Chen, Bora Lim, Devon Lawson, Nicholas Navin, Kai Kessenbrock. A spatially resolved single cell atlas of the human breast [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5702.