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 测序来编制人类乳腺细胞图谱，该图谱由 55 名接受过乳房缩小成形术或风险降低乳房切除术的捐赠者组成。我们从超过 800,000 个细胞中鉴定出跨上皮、免疫和基质区室的 41 个细胞亚群。这些不同簇的贡献根据组织的自然历史而变化。已知年龄、胎次和种系突变会调节患乳腺癌的风险，它们以不同的方式影响乳房的稳态细胞状态。我们发现来自BRCA1 或 BRCA2携带者的免疫细胞具有明显的基因表达特征，表明潜在的免疫衰竭，这一点通过免疫组织化学得到了验证。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。该图集是一个丰富的资源，可用于为乳腺癌早期检测和预防的新方法提供信息。