دورية أكاديمية
أعرض في EDS

A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells.

التفاصيل البيبلوغرافية
العنوان: A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells.
المؤلفون: Najafabadi MG; Department of Oncology, University of Cambridge, Cambridge, UK., Gray GK; Department of Cell Biology, Harvard Medical School (HMS), Boston, MA, USA., Kong LR; MRC Cancer Unit, University of Cambridge, Cambridge, UK.; The Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Pharmacology, NUS School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Centre for Cancer Research, National University of Singapore, Singapore, Singapore., Gupta K; MRC Cancer Unit, University of Cambridge, Cambridge, UK.; The Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; NUS Centre for Cancer Research, National University of Singapore, Singapore, Singapore., Perera D; MRC Cancer Unit, University of Cambridge, Cambridge, UK., Naylor H; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Brugge JS; Department of Cell Biology, Harvard Medical School (HMS), Boston, MA, USA., Venkitaraman AR; MRC Cancer Unit, University of Cambridge, Cambridge, UK. arv22@nus.edu.sg.; The Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. arv22@nus.edu.sg.; Institute of Molecular & Cellular Biology Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore. arv22@nus.edu.sg., Shehata M; Department of Oncology, University of Cambridge, Cambridge, UK. ms2140@cam.ac.uk.; MRC Cancer Unit, University of Cambridge, Cambridge, UK. ms2140@cam.ac.uk.
المصدر: Nature communications [Nat Commun] 2023 Aug 25; Vol. 14 (1), pp. 5206. Date of Electronic Publication: 2023 Aug 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Epithelial Cells* , Interferon Type I*, Cell Proliferation ; Cell Cycle ; Gene Expression
مستخلص: Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations. Here, we report that monoallelic Brca2 mut/WT mammary organoids subjected to replication stress activate a transcriptional response that selectively expands Brca2 mut/WT luminal cells lacking hormone receptor expression (HR-). While CyTOF analyses reveal comparable epithelial compositions among wildtype and Brca2 mut/WT mammary glands, Brca2 mut/WT HR- luminal cells exhibit greater organoid formation and preferentially survive and expand under replication stress. ScRNA-seq analysis corroborates the expansion of HR- luminal cells which express elevated transcript levels of Tetraspanin-8 (Tspan8) and Thrsp, plus pathways implicated in replication stress survival including Type I interferon responses. Notably, CRISPR/Cas9-mediated deletion of Tspan8 or Thrsp prevents Brca2 mut/WT HR- luminal cell expansion. Our findings indicate that Brca2 mut/WT cells activate a transcriptional response after replication stress that preferentially favours outgrowth of HR- luminal cells through the expression of interferon-responsive and mammary alveolar genes.
(© 2023. Springer Nature Limited.)
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المشرفين على المادة: 0 (Interferon Type I)
تواريخ الأحداث: Date Created: 20230825 Date Completed: 20230828 Latest Revision: 20231119
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10457340
DOI: 10.1038/s41467-023-40956-w
PMID: 37626143
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-40956-w