英国剑桥大学Walid T. Khaled等研究人员合作发现，单细胞图谱绘制出成年人类乳房的细胞平衡变化。这一研究成果于2024年3月28日在线发表在国际学术期刊《自然—遗传学》上。

研究人员利用单细胞RNA测序技术编制了人类乳腺细胞图谱，该图谱由5 位接受乳房缩小整形术或风险降低乳房切除术的供体采集而成。研究人员从80多万个细胞中识别出了41个细胞亚群，涵盖上皮细胞、免疫细胞和基质细胞。这些不同细胞群的贡献因组织的自然史而异。已知年龄、妊娠期和生殖突变会影响乳腺癌的发病风险，但它们以不同的方式影响着乳腺的细胞平衡状态。

研究人员发现，BRCA1或BRCA2携带者的免疫细胞具有不同的基因表达特征，表明可能出现免疫衰竭，这一点已通过免疫组化得到验证。这表明，免疫逃逸机制可能在肿瘤发生的早期就在非癌组织中显现出来。该图谱资源丰富，可为乳腺癌的早期检测和预防提供新方法。

附：英文原文

Title: A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast

Author: Reed, Austin D., Pensa, Sara, Steif, Adi, Stenning, Jack, Kunz, Daniel J., Porter, Linsey J., Hua, Kui, He, Peng, Twigger, Alecia-Jane, Siu, Abigail J. Q., Kania, Katarzyna, Barrow-McGee, Rachel, Goulding, Iain, Gomm, Jennifer J., Speirs, Valerie, Jones, J Louise, Marioni, John C., Khaled, Walid T.

Issue&Volume: 2024-03-28

Abstract: Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.

DOI: 10.1038/s41588-024-01688-9

Source: https://www.nature.com/articles/s41588-024-01688-9