Skip to main content
Premium Trial:

Request an Annual Quote

Human Breast Cell Atlas Reveals Different Cell Types, States

NEW YORK — Researchers have created the first comprehensive spatially resolved single-cell genomic atlas of human breast tissue.

In a paper published in Nature on Wednesday, researchers from MD Anderson Cancer Center and elsewhere presented their findings on various breast cell types, cell states, and differences in breast tissues between ethnicities.

Co-corresponding author Nicholas Navin, a professor at MD Anderson, compared the atlas to the Human Genome Project, but for the breast. "We can now look at breast cancers and compare them with a baseline," he said.

Human breast tissue consists of four major regions: lobular units, ducts, connective tissue, and adipose tissue. While most previous studies focused on epithelial cells, which have been implicated in breast cancer, the authors noted that their goal was to focus on all cell types in the breast.

For their study, which started seven years ago, the researchers collected 220 fresh breast tissue samples from 132 women, including those having breast reduction surgery, undergoing prophylactic breast removal, and having breast cancer surgery, where they obtained tissue from the unaffected breast. While almost half the women were Caucasian, more than 40 percent were African American, and 13 percent had other ethnic backgrounds.

A subset of the samples — 167 tissue samples collected from 126 women — were subjected to single-cell RNA sequencing analysis using 10x Genomics technology, generating data for almost 715,000 cells. This helped identify 10 major cell type clusters, including three epithelial cell types, lymphatic and vascular endothelial cells, three immune cell types (T cells, B cells, and myeloid cells), as well as fibroblast and perivascular mesenchymal cell types.

Since adipocytes were not detected by scRNA-seq due to their large size, the researchers also performed single-nucleus RNA-seq on more than 117,000 cells, which identified clusters of adipocytes and mast cells, in addition to the other cell types.

In addition to the single-cell analyses, the researchers also used three technologies to investigate the spatial organization of cell types in tissue slices from a total of 23 women, including spatial transcriptomics from 10x Genomics, targeted single-molecule RNA fluorescence in situ hybridization (smFISH) from Resolve Biosciences, and, for protein analysis, co-detection by indexing (CODEX) from Akoya Biosciences. They also used Vizgen's MERFISH to resolve the spatial distribution of epithelial cell states.

Overall, their study reported 12 major cell types and 58 unique cell states that were organized into four major spatial tissue domains. It also identified changes in breast tissue architecture that corresponded to ethnicity, age, and menopause. In addition, there weren't many differences in tissue samples between pregnant and non-pregnant women, the authors said. "This is an important finding, as it really tells you that not all breast tissues are the same," Navin said. 

The presence of high numbers of immune cells was especially surprising, he said. Breast immune cells were previously studied in the context of breast cancers, he added, however it was unknown until now that these cells are present in high numbers even in normal breast tissue.

In subsequent metadata ethnicity analyses, the researchers noted stark differences between breast tissues of Caucasian and African women. Fibroblasts, myeloid, and B cells were elevated in African women, and they had increases of 13 cell states, compared with Caucasian women.

Overall, the findings have implications for early cancer detection and the development of new therapeutics. "The presence of such high numbers of immune cells could open new ways to developing immunotherapies," Navin said.

The project was a part of the Human Cell Atlas initiative, which began in 2016. Earlier this month, researchers from Finland published an atlas of the human lung.

Navin noted that future studies will need to delineate the functional roles of the newly discovered cell states, which could take over a decade. Going forward, he plans to include samples from women of other ethnicities to make the atlas more inclusive and usable.