澳大利亚加文医学研究所Alexander Swarbrick团队绘制出人类乳腺癌的单细胞和空间分辨率图谱。这一研究成果发表在2021年9月6日出版的国际学术期刊《自然—遗传学》上。

研究人员介绍了人类乳腺癌的单细胞和空间分辨率转录组学分析。研究人员开发了一种单细胞的内在亚型分类方法（SCSubtype）来揭示反复出现的肿瘤细胞异质性。利用测序的转录组和表位的细胞索引（CITE-seq）进行免疫分型，研究人员提供了高分辨率的免疫图谱，包括与临床结果相关的新的PD-L1/PD-L2⁺巨噬细胞群。间质细胞通过在三个主要谱系内的分化显示了不同的功能和细胞表面蛋白的表达。基质免疫微环境在肿瘤中被空间性组织，这提供了对抗肿瘤免疫调节的见解。

利用单细胞特征，研究人员对大型乳腺癌队列进行了分解，并将其分为九个群组，称为 "生态型"，具有独特的细胞组成和临床结果。这项研究为乳腺癌的细胞结构提供了一个全面的转录图谱。

据悉，乳腺癌是复杂的细胞生态系统，其中异型的相互作用在疾病的发展和对治疗的反应中起着核心作用。然而，人们对其细胞组成和组织的了解是有限的。

附：英文原文

Title: A single-cell and spatially resolved atlas of human breast cancers

Author: Wu, Sunny Z., Al-Eryani, Ghamdan, Roden, Daniel Lee, Junankar, Simon, Harvey, Kate, Andersson, Alma, Thennavan, Aatish, Wang, Chenfei, Torpy, James R., Bartonicek, Nenad, Wang, Taopeng, Larsson, Ludvig, Kaczorowski, Dominik, Weisenfeld, Neil I., Uytingco, Cedric R., Chew, Jennifer G., Bent, Zachary W., Chan, Chia-Ling, Gnanasambandapillai, Vikkitharan, Dutertre, Charles-Antoine, Gluch, Laurence, Hui, Mun N., Beith, Jane, Parker, Andrew, Robbins, Elizabeth, Segara, Davendra, Cooper, Caroline, Mak, Cindy, Chan, Belinda, Warrier, Sanjay, Ginhoux, Florent, Millar, Ewan, Powell, Joseph E., Williams, Stephen R., Liu, X. Shirley, OToole, Sandra, Lim, Elgene, Lundeberg, Joakim, Perou, Charles M., Swarbrick, Alexander

Issue&Volume: 2021-09-06

Abstract: Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.

DOI: 10.1038/s41588-021-00911-1

Source: https://www.nature.com/articles/s41588-021-00911-1