Nature: Largest-ever atlas of normal human breast cells brings unprecedented new insights into breast biology

In a new study, researchers from research institutions including the University of Texas MD Anderson Cancer Center, the University of California, Irvine, and Baylor College of Medicine constructed the world’s largest and most comprehensive atlas of normal breast tissue, providing An unprecedented understanding of breast biology may help identify therapeutic targets for diseases such as breast cancer. Relevant research results will be published online in the journal Nature on June 28, 2023. The title of the paper is “A spatially resolved single-cell genomic atlas
of the adult human breast”。

The Human Breast Cell Atlas analyzed more than 714,000 cells from 126 women using single-cell and spatial genomics approaches. This breast cell atlas highlights 12 major cell types and 58 biological cell states, and identifies differences according to race, age, and menopausal status in healthy women.

Co-corresponding author of the paper, Dr. Nicholas Navin, director of systems biology at the University of Texas MD Anderson Cancer Center, said, “We are very pleased to see the completion of this monumental seven-year project. We expect this tool to be very useful for those studying breast cancer and other diseases such as mastitis, as well as failures of mammary gland development and lactation.”

The new study was led by Navin, Dr. Kai Kessenbrock and Devon Lawson of UC Irvine, and Dr. Bora Lim and Dr. Alastair Thompson of Baylor College of Medicine. The project is a global Human Cell Atlas (Human Cell Atlas) project supported by the Chan Zuckerberg Initiative (Chan Zuckerberg Initiative).
Atlas) consortium that leverages the latest technologies to build cellular reference atlases for every organ system in the human body.

The human body contains approximately 200 different cell types, 12 of which are found in normal breast tissue. Previous studies of breast tissue have focused on epithelial cells because these cells are known to give rise to cancer, but non-epithelial cell types of the breast have not been studied in depth using genomics approaches.

Modern tools, such as single-cell sequencing and spatial mapping, enabled these authors to classify in high detail 12 major clusters of cell types, including three types of epithelial cells, lymphocytes, vascular cells, T cells, B cells, myeloid cells, adipocytes, mast cells, fibroblasts, and perivascular cells.

For the new study, the authors collected and studied 220 breast tissue samples from 132 women who had undergone breast reduction or mastectomy. Of these women, 46 percent were white, 41 percent were African American, 7 percent were Hispanic, and 6 percent were of unknown ethnicity. The samples were collected at four institutions, including the University of Texas MD Anderson Cancer Center, the University of California, Irvine, Baylor College of Medicine and St. Luke’s Hospital.

This wide-ranging dataset of normal breast cell types and their different states in women also takes into account individual factors, including race, age, body mass index (BMI), obesity, menopausal status, and number of pregnancies and births, providing Rich information, a powerful resource for the research community.

Spatial mapping highlights four major cellular regions, unexpected immune cell populations

Spatial mapping techniques to construct cell atlases in tissue contexts allowed the authors to observe the RNA and protein composition of these samples to understand how and where different types of cells are distributed.

These techniques address the composition of known cell types and novel cell states in four major regions of the mammary gland, including the lobular milk-producing area, the ductal area that transports milk, composed of fibroblasts, and Connective tissue and adipose area mainly composed of adipose tissue.

The authors were surprised to find that 16.7 percent of all cells found in normal breast tissue consisted of immune cells, including three main types: myeloid cells, natural killer T cells, and B cells. Scientists previously thought that immune cells were rarely found in normal tissue.

Furthermore, these immune cells were predominantly located around ducts and lobules in three of the major tissue regions. Navin explained that understanding the nuances of these different immune cells may help in the development of more effective immunotherapies for certain subtypes of breast cancer, as well as in determining their role in breast cancer progression.

The authors also found unexpectedly high numbers (7.4%) of vascular pericytes, including pericytes, which regulate blood flow from capillaries into tissues, and vascular smooth muscle cells, which regulate arterial constriction.

Age, menopause and race play roles in different cell types and states

The new study reveals striking differences in breast tissue composition and cellular state depending on race, age and menopausal status. For example, African-American women are disproportionately affected by aggressive breast cancer subtypes—such as triple-negative breast cancer and inflammatory breast cancer—but little is known about the underlying reasons for this difference. With further research, the differences in baseline cell state seen in breast tissue from African-American and Caucasian women could lead to the discovery of potential markers that predict cancer risk.

In addition, there were marked differences in breast tissue in women over 50 years of age compared with younger women, and differences in cellular status also depended on menopausal status. Obesity, BMI, pregnancy status, and breast density also showed some smaller differences in cell type and cell state changes.

The authors note that more research is needed to further understand the many functional roles in these cell states, and to focus on other factors that may greatly advance knowledge of human breast biology and disease.

The Human Breast Cell Atlas project is ongoing and actively recruiting participants to build and improve the dataset built in this new study, but it is now freely accessible to scientists.

References:

2. Largest-ever atlas of normal breast cells brings unprecedented insights into mammary biology

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General Assembly Information

Meeting Name |

2023 The Sixth Single-Cell Multi-Omics Research and Clinical Application Summit

meeting time |

September 14-15, 2023

meeting place |

Radisson Blu Hotel Shanghai Hongqiao West

Assembly scale |

800 people

organizer

|

bio valley

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