The world’s largest breast cell atlas reveals new insights into mammary biology

The MD Anderson study maps normal breast cells, which could have an impact on cancer and other disorders.

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Researchers from The University of Texas MD Anderson Cancer Centre, University of California, Irvine, and Baylor College of Medicine have generated the world’s largest and most described map of normal breast tissue

The Human Breast Cell Atlas, published in Nature, profiled nearly 714,000 cells from 126 women using single-cell and spatial genomic approaches. The atlas emphasizes 12 primary cell types and 58 natural cell states in healthy women. It indicates variances based on ethnicity, age, and menopausal status.

The researchers analyzed 220 breast tissue samples from 132 patients with breast reduction or mastectomy surgery. Individual characteristics such as ethnicity, age, BMI, obesity, menopause status, pregnancy, and number of births were also considered in the study.

Senior corresponding author Nicholas Navin, Ph.D., chair of Systems Biology at MD Anderson, said, “We are thrilled to see the completion of this monumental seven-year project. We were able to leverage many technologies to define, in a very granular way, all the different cell types and cell states in each of the main areas of the breast. We expect this tool will be highly useful for anyone studying breast cancer and other diseases such as mastitis, breast development, and lactation failure.”

The research is part of the global Human Cell Atlas collaboration, which employs cutting-edge technology to create cellular reference maps for every organ system in the human body and is funded by the Chan Zuckerberg Initiative (CZI). 

There are over 200 distinct cell types in the human body, 12 of which are found in normal breast tissue. Previous research on breast tissue has mostly focused on epithelial cells known to cause cancer. However, non-epithelial cell types have yet to be investigated in-depth utilizing genomic techniques.

The researchers were able to perform a highly detailed classification of twelve major cell type clusters using modern tools such as single-cell sequencing and spatial mapping, which included three types of epithelial cells, lymphatic cells, vascular cells, T cells, B cells, myeloid cells, adipocytes, mast cells, fibroblasts, and perivascular cells.

Researchers gathered and analyzed 220 breast tissue samples from 132 individuals undergoing breast reduction or mastectomy surgery for this study. These ladies were 46% Caucasian, 41% African American, 7% Hispanic, and 6% of unknown origin. MD Anderson, UC Irvine, the Dan L Duncan Comprehensive Cancer Centre at Baylor St. Luke’s Medical Centre, and Harris Health System gathered samples. 

Obesity, menopause status, pregnancy, and number of births, offer a plethora of information that serves as a valuable resource for researchers.

Spatial mapping identifies four primary cell regions and surprises immune cell populations. Researchers used spatial mapping techniques to generate a map of the cells within the tissue environment to investigate the RNA and protein content of the samples to find how and where the different cell types resided.  

These techniques determined the composition of known cell types and new cell states in the four major regions of the breast that are currently known, including lobular milk-producing areas, ductal areas that transport milk, connective tissue composed of fibroblasts, and adipose areas composed primarily of fatty tissue.

According to spatial mapping methodologies, immune cells comprising myeloid, natural killer (NK) T cells, and B cells comprised 16.7% of all cells observed in normal breast tissue. Understanding the intricacies of these different immune cells could aid in developing more effective immunotherapies for particular subtypes of breast cancer and clarify their function in the evolution of the disease. 

The researchers also discovered an unusually high percentage (7.4%) of perivascular cells, which included pericytes and vascular smooth muscle cells.

Age, menopause, and ethnicity impact certain cell types and states. The researchers discovered significant changes in breast tissue composition and cell states based on ethnicity, age, and menopausal status. Additional studies could identify promising markers for cancer risk prediction. 

According to the authors, more research is needed to understand better the functional relevance of many of these cell states and to focus on other elements that could considerably expand our understanding of human breast biology and illness.

The Human Breast Cell Atlas project is funded by the Chan Zuckerberg Initiative, the National Cancer Institute.

Journal Reference:

  1. Kumar, T., Nee, K., Wei, R. et al. A spatially resolved single-cell genomic atlas of the adult human breast. Nature. DOI: 10.1038/s41586-023-06252-9
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