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人类乳腺图谱整合单细胞蛋白质组学和转录组学。

A human breast atlas integrating single-cell proteomics and transcriptomics.

机构信息

Department of Cell Biology, Harvard Medical School (HMS), Boston, MA 02115, USA.

Department of Cell Biology, Harvard Medical School (HMS), Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA 02115, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

出版信息

Dev Cell. 2022 Jun 6;57(11):1400-1420.e7. doi: 10.1016/j.devcel.2022.05.003. Epub 2022 May 25.


DOI:10.1016/j.devcel.2022.05.003
PMID:35617956
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9202341/
Abstract

The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells termed basal-luminal (BL) cells, which exhibit poor transcriptional lineage fidelity, accumulate with age, and carry a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell-subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states.

摘要

乳房是一个动态的器官,其对生理和病理生理条件的反应改变了其疾病易感性,但这些临床变量对细胞状态的具体影响仍未得到充分注释。我们通过整合单细胞 RNA 测序、质谱细胞术和周期性免疫荧光技术,呈现了一个统一的、高分辨率的乳房图谱,涵盖了无数的状态。我们在肺泡、激素感应和基底上皮谱系内定义了细胞亚型,描绘了几个亚型与癌症风险因素(包括年龄、产次和 BRCA2 种系突变)的关联。特别值得关注的是一组被称为基底-腔(BL)细胞的肺泡细胞,它们表现出较差的转录谱系保真度,随年龄增长而积累,并带有与基底样乳腺癌相关的基因特征。我们进一步利用培养基耗竭方法来鉴定调节类器官中细胞亚型比例的分子因素。这些数据是一个丰富的资源,可以阐明不同的乳腺细胞状态。

相似文献

[1]
A human breast atlas integrating single-cell proteomics and transcriptomics.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
BRCA1 mutation influences progesterone response in human benign mammary organoids.

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[9]
New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.

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[10]
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[2]
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[3]
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[4]
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[5]
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Br J Cancer. 2025-7-2

[6]
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Nat Cell Biol. 2025-6-27

[7]
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[8]
Volumetric printed biomimetic scaffolds support in vitro lactation of human milk-derived mammary epithelial cells.

Sci Adv. 2025-6-6

[9]
Accurate Transcription Factor Activity Inference to Decipher Cell Identity from Single-Cell Transcriptomic Data with MetaTF.

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[10]
senescence and senolytic functional assays.

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本文引用的文献

[1]
Evidence for accelerated aging in mammary epithelia of women carrying germline or mutations.

Nat Aging. 2021-9

[2]
Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk.

Nat Commun. 2022-1-28

[3]
Joint single-cell measurements of nuclear proteins and RNA in vivo.

Nat Methods. 2021-10

[4]
Impaired Lactation: Review of Delayed Lactogenesis and Insufficient Lactation.

J Midwifery Womens Health. 2021-9

[5]
Selective progesterone receptor blockade prevents BRCA1-associated mouse mammary tumors through modulation of epithelial and stromal genes.

Cancer Lett. 2021-11-1

[6]
The preventive effect of breastfeeding against ovarian cancer in BRCA1 and BRCA2 mutation carriers: A systematic review and meta-analysis.

Gynecol Oncol. 2021-10

[7]
Integrated analysis of multimodal single-cell data.

Cell. 2021-6-24

[8]
Mammary epithelial cells have lineage-rooted metabolic identities.

Nat Metab. 2021-5

[9]
Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland.

J Mammary Gland Biol Neoplasia. 2021-3

[10]
A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.

EMBO J. 2021-6-1

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