@article{222f0a619fad4c249d0644f0c9a31493,
title = "Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages",
abstract = "Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, we identify key genes defining the basal-like (SOX6 and KCNQ3) and luminal A/B (FAM155A and LRP1B) lineages. Exhausted CTLA4-expressing CD8+ T cells were enriched in basal-like BC, suggesting an altered means of immune dysfunction. These findings demonstrate analysis of paired transcription and chromatin accessibility at the single-cell level is a powerful tool for investigating cancer lineage and highlight transcriptional networks that define basal and luminal BC lineages.",
author = "Iglesia, {Michael D.} and Jayasinghe, {Reyka G.} and Siqi Chen and Terekhanova, {Nadezhda V.} and Herndon, {John M.} and Erik Storrs and Alla Karpova and Zhou, {Daniel Cui} and {Naser Al Deen}, Nataly and Shinkle, {Andrew T.} and Lu, {Rita Jui Hsien} and Wagma Caravan and Andrew Houston and Yanyan Zhao and Kazuhito Sato and Preet Lal and Cherease Street and {Martins Rodrigues}, Fernanda and Southard-Smith, {Austin N.} and {Targino da Costa}, {Andr{\'e} Luiz N.} and Houxiang Zhu and Mo, {Chia Kuei} and Lisa Crowson and Fulton, {Robert S.} and Wyczalkowski, {Matthew A.} and Fronick, {Catrina C.} and Fulton, {Lucinda A.} and Hua Sun and Davies, {Sherri R.} and Appelbaum, {Elizabeth L.} and Chasnoff, {Sara E.} and Madelyn Carmody and Candace Brooks and Ruiyang Liu and Wendl, {Michael C.} and Clara Oh and Diane Bender and Carlos Cruchaga and Oscar Harari and Andrea Bredemeyer and Kory Lavine and Ron Bose and Julie Margenthaler and Held, {Jason M.} and Samuel Achilefu and Foluso Ademuyiwa and Rebecca Aft and Cynthia Ma and Colditz, {Graham A.} and Tao Ju and Oh, {Stephen T.} and James Fitzpatrick and Hwang, {E. Shelley} and Shoghi, {Kooresh I.} and Chheda, {Milan G.} and Veis, {Deborah J.} and Feng Chen and Fields, {Ryan C.} and Gillanders, {William E.} and Li Ding",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
month = nov,
doi = "10.1038/s43018-024-00773-6",
language = "English",
volume = "5",
pages = "1713--1736",
journal = "Nature Cancer",
issn = "2662-1347",
number = "11",
}