The Human Breast Cell Atlas

The Project

The anatomy and histopathology of the human breast has been studied for many decades and has provided insights into development, lactation and disease. More recently normal breast tissues have been profiled with molecular and genomic methods, which have largely focused on the epithelial cells. To date, an unbiased and comprehensive analysis of all cell types and their biological subtypes (cell states) has remained lacking. In this Human Breast Cell Atlas (HBCA) project, we aimed to generate a comprehensive reference of cell types and cell states in the adult human breast tissues using single cell and spatial genomic methods. Here, we profiled breast tissues from over 100 women with diverse biological states (parity, menopause, age, ethnicity), which has identified 12 major cell types and over 60 biological cell states. These cell types and cell states are spatially organized into four major areas of the breast: ductal, lobular, adipose and connective regions. Our analysis has revealed abundant pericyte, endothelial and immune cell populations in normal breast, as well as highly diverse luminal epithelial cell states. Our spatial mapping using multiple technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells in the ducts and lobules, as well as distinct epithelial cell state differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of adult normal breast tissue for studying mammary biology and disease states such as breast cancer. We are extremely grateful to all of the women who have selflessly donated their tissues to this project and provided this data to the research community. All of the single cell and spatial data from this project are available for open access via our data portals. This project has also established optimized tissue dissociation protocols and data analysis code that are freely available for download. Our project is part of the greater Human Cell Atlas (HCA) effort and has been generously funded by the Chan-Zuckerberg Initiative over many years. In addition to our HBCA project, there are several other ongoing human breast atlas projects that focus on different areas.