A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells.
A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells.
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DOI：
10.1016/j.xcrm.2021.100219
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发表时间：
2021-03-16
期刊：
影响因子：
--
通讯作者：
Nakshatri H
中科院分区：
文献类型：
--
作者：
Bhat-Nakshatri P;Gao H;Sheng L;McGuire PC;Xuei X;Wan J;Liu Y;Althouse SK;Colter A;Sandusky G;Storniolo AM;Nakshatri H
单细胞 RNA 测序 (scRNA-seq) 是一项不断发展的技术，用于阐明成人器官的细胞结构。先前对乳腺组织进行的 scRNA 测序使用的是乳房成形术样本，这些样本通常存在组织学异常。我们报告了一种快速组织收集/处理方案，用于对健康女性的乳腺活检进行 scRNA-seq 并鉴定 23 个乳腺上皮细胞簇。来自这些簇的假定细胞起源特征被应用于分析约 3,000 种乳腺癌的转录组。来自成熟管腔细胞簇的基因特征在约 68% 的乳腺癌中富集，而来自管腔祖细胞簇的特征在约 20% 的乳腺癌中富集。管腔祖细胞簇衍生的特征在 HER2+ 中过度表达，但在其他亚型中则不然，与不良结果相关。我们将 TBX3 和 PDK4 确定为在正常乳房中与雌激素受体 (ER) 共表达的基因，并且它们在超过 550 种乳腺癌中的表达分析使得能够对 ER+ 乳腺癌进行与预后相关的亚分类。健康乳房含有 23 个上皮细胞亚群乳腺癌可能起源于 3 个管腔成熟亚群和 1 个祖细胞亚群 TBX3 和 PDK4，与雌激素受体 (ER) 共表达，将 ER+ 乳腺癌亚分类 Bhat-Nakshatri 等人。描述健康乳房中的单细胞图谱并记录 23 个上皮细胞亚群。尽管通过实验验证肿瘤起源细胞在技术上具有挑战性，但对富含亚簇的基因特征与乳腺肿瘤转录组的重叠分析揭示了乳腺癌中分化的管腔亚簇衍生特征的显性表现。
Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers. Healthy breast contains 23 subclusters of epithelial cells Breast cancers may originate from 3 luminal mature and 1 progenitor subclusters TBX3 and PDK4, co-expressed with estrogen receptor (ER), subclassify ER+ breast cancers Bhat-Nakshatri et al. describe the single-cell atlas and document 23 epithelial cell subclusters in the healthy breast. Although experimentally validating cell of origin of a tumor is technically challenging, overlap analysis of subcluster-enriched gene signatures with breast tumor transcriptomes revealed dominant representation of differentiated luminal subclusters-derived signatures in breast cancers.
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