GS1-02:构建人类乳腺细胞图谱

Tk Seth, S. Bai, M. Hu, Emi Sei, Al Wood, J. Wiley, Huiqin Chen, A. Contreras, M. Teshome, B. Lim, N. Navin
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引用次数: 0

摘要

人类乳房组织由小叶组成,这些小叶连接着一个复杂的导管网络,在进化过程中,这些导管被设计用来生产和输送乳汁,以滋养后代。组织病理学已经根据形态学特征确定了10种主要的细胞类型,但在细胞状态(反映不同生物学功能的细胞类型的转录程序)方面提供的信息有限。在这项研究中,我们利用单细胞RNA测序方法生成了正常人类乳房的无偏细胞图谱,以确定细胞类型和细胞状态。我们对11名乳腺切除术后病理正常的女性的31442个间质细胞进行了39个基于微滴的单细胞RNA测序。无偏表达分析鉴定出三种主要的细胞类型:上皮细胞(管状细胞和基底细胞)、成纤维细胞和内皮细胞,此外还有几种次要的细胞类型:巨噬细胞、t细胞、自然杀伤细胞、周细胞和平滑肌细胞。这些细胞类型的细胞状态分析揭示了不同的转录程序在管腔上皮细胞(激素受体阳性和分泌),基底上皮细胞(肌上皮或基底样),内皮细胞(淋巴或血管),巨噬细胞(M1或M2)和成纤维细胞(三个亚群),并提供了了解每种细胞类型的祖细胞。这些数据为研究界提供了有价值的参考,并将为正常细胞类型如何在肿瘤微环境中转化以促进或抑制乳腺癌的进展提供新的见解。引用格式:Seth TK, Bai S, Hu M, Sei E, Wood A, Wiley J, Chen H, Contreras A, Teshome M, Lim B, Navin NE。迈向人类乳腺细胞图谱[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志,2019;79(4增刊):摘要nr GS1-02。
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Abstract GS1-02: Towards a human breast cell atlas
The human breast tissue consists of lobules connected to a complex network of ducts that are evolutionarily designed to produce and transport milk to nourish offspring. Histopathology has identified 10 major cell types based on morphological features but have provided limited information on cell states - the transcriptional programs of cell types that reflect different biological functions. In this study, we have generated an unbiased 9cell atlas9 of the normal human breast to define the cell types and cell states using single cell RNA sequencing methods. We performed 39 microdroplet based single cell RNA sequencing of 31,442 stromal cells from 11 women with pathologically normal breast tissues that were collected from mastectomies. Unbiased expression analysis identified three major cell types: epithelial cells (luminal and basal), fibroblasts and endothelial cells, in addition to several minor cell types: macrophages, T-cells, natural killer cells, pericytes and smooth muscle cells. Analysis of cell states of these cell types revealed different transcriptional programs in luminal epithelial cells (hormone receptor positive and secretory), basal epithelial cells (myoepithelial or basement-like), endothelial cells (lymphatic or vascular), macrophages (M1 or M2) and fibroblasts (three subgroups) and provided insight into progenitors of each cell types. These data provide a valuable reference for the research community and will provide new insights into how normal cell types are transformed in the tumor microenvironment to promote or inhibit the progression of breast cancer. Citation Format: Seth TK, Bai S, Hu M, Sei E, Wood A, Wiley J, Chen H, Contreras A, Teshome M, Lim B, Navin NE. Towards a human breast cell atlas [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-02.
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Abstract GS4-02: E2112: Randomized phase 3 trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. A trial of the ECOG-ACRIN cancer research group Abstract GS3-07: Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort Abstract GS2-03: Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27,000 patients Abstract GS5-01: A randomized community-based trial of an angiotensin converting enzyme inhibitor, lisinopril or a beta blocker, carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving adjuvant trastuzumab Abstract GS4-02: Regional lymph node irradiation in early stage breast cancer: An EBCTCG meta-analysis of 13,000 women in 14 trials
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