Project description:This study presents a single cell and spatially resolved transcriptomics analysis of human breast cancers. We develop a single cell method of intrinsic subtype classification (scSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using CITE-Seq provides high-resolution immune profiles, including novel PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell surface protein expression through differentiation within 3 major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into anti-tumor immune regulation. Using single cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.
Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.
Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.