Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry

dc.contributor.authorBhat-Nakshatri, Poornima
dc.contributor.authorGao, Hongyu
dc.contributor.authorKhatpe, Aditi S.
dc.contributor.authorAdebayo, Adedeji K.
dc.contributor.authorMcGuire, Patrick C.
dc.contributor.authorErdogan, Cihat
dc.contributor.authorChen, Duojiao
dc.contributor.authorJiang, Guanglong
dc.contributor.authorNew, Felicia
dc.contributor.authorGerman, Rana
dc.contributor.authorEmmert, Lydia
dc.contributor.authorSandusky, George
dc.contributor.authorStorniolo, Anna Maria
dc.contributor.authorLiu, Yunlong
dc.contributor.authorNakshatri, Harikrishna
dc.contributor.departmentSurgery, School of Medicine
dc.date.accessioned2025-05-15T15:38:17Z
dc.date.available2025-05-15T15:38:17Z
dc.date.issued2024
dc.description.abstractSingle-nucleus analysis allows robust cell-type classification and helps to establish relationships between chromatin accessibility and cell-type-specific gene expression. Here, using samples from 92 women of several genetic ancestries, we developed a comprehensive chromatin accessibility and gene expression atlas of the breast tissue. Integrated analysis revealed ten distinct cell types, including three major epithelial subtypes (luminal hormone sensing, luminal adaptive secretory precursor (LASP) and basal-myoepithelial), two endothelial and adipocyte subtypes, fibroblasts, T cells, and macrophages. In addition to the known cell identity genes FOXA1 (luminal hormone sensing), EHF and ELF5 (LASP), TP63 and KRT14 (basal-myoepithelial), epithelial subtypes displayed several uncharacterized markers and inferred gene regulatory networks. By integrating breast epithelial cell gene expression signatures with spatial transcriptomics, we identified gene expression and signaling differences between lobular and ductal epithelial cells and age-associated changes in signaling networks. LASP cells and fibroblasts showed genetic ancestry-dependent variability. An estrogen receptor-positive subpopulation of LASP cells with alveolar progenitor cell state was enriched in women of Indigenous American ancestry. Fibroblasts from breast tissues of women of African and European ancestry clustered differently, with accompanying gene expression differences. Collectively, these data provide a vital resource for further exploring genetic ancestry-dependent variability in healthy breast biology.
dc.eprint.versionFinal published version
dc.identifier.citationBhat-Nakshatri P, Gao H, Khatpe AS, et al. Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry [published correction appears in Nat Med. 2025 Apr 7. doi: 10.1038/s41591-025-03681-z.]. Nat Med. 2024;30(12):3482-3494. doi:10.1038/s41591-024-03011-9
dc.identifier.urihttps://hdl.handle.net/1805/48176
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41591-024-03011-9
dc.relation.journalNature Medicine
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectTranslational research
dc.subjectBreast cancer
dc.subjectChromatin
dc.subjectFibroblasts
dc.titleSingle-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry
dc.typeArticle
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