1. Single cell transcriptome atlas of mouse mammary epithelial cells across development
- Author
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Jane E. Visvader, Felicity C. Jackling, Gordon K. Smyth, Geoffrey J. Lindeman, Paul Timpson, Yunshun Chen, Caleb A. Dawson, Lexie Prokopuk, François Vaillant, Bianca D. Capaldo, Bhupinder Pal, Xiaoyu Song, and Michael J. G. Milevskiy
- Subjects
Morphogenesis ,Progenitors ,Biology ,Transcriptome ,Mice ,Single cell transcriptome ,03 medical and health sciences ,Mammary Glands, Animal ,0302 clinical medicine ,Terminal end bud ,Animals ,Cell Lineage ,Progenitor cell ,RC254-282 ,Uncategorized ,030304 developmental biology ,Progenitor ,Chromatin accessibility ,0303 health sciences ,Stem Cells ,Embryogenesis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Epithelial Cells ,Chromatin Assembly and Disassembly ,Molecular heterogeneity ,Chromatin ,Cell biology ,Mammary gland development ,Mammary Epithelium ,030220 oncology & carcinogenesis ,Single-Cell Analysis ,Stem cell ,Research Article - Abstract
Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.
- Published
- 2021