Department of Pharmacology, University of Cambridge, Cambridge, UK.
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Nat Genet. 2024 Apr;56(4):652-662. doi: 10.1038/s41588-024-01688-9. Epub 2024 Mar 28.
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.
在这里，我们使用单细胞 RNA 测序技术，从 55 位接受过缩乳术或预防性乳房切除术的捐赠者中汇编了一个人类乳腺细胞图谱。我们从超过 80 万个细胞中鉴定出了上皮、免疫和基质区室中的 41 个细胞亚群。这些不同簇的贡献根据组织的自然史而有所不同。年龄、产次和种系突变，已知会调节患乳腺癌的风险，以不同的方式影响乳腺的稳态细胞状态。我们发现，BRCA1 或 BRCA2 携带者的免疫细胞具有独特的基因表达特征，表明存在潜在的免疫耗竭，这通过免疫组织化学得到了验证。这表明，在肿瘤起始的早期，免疫逃避机制可能在非癌组织中表现出来。这个图谱是一个丰富的资源，可以用于为早期检测和预防乳腺癌提供新的方法。
