Single cell transcriptome atlas of mouse mammary epithelial cells across development
Details
Publication Year 2021-06-29, Volume 23, Issue #1, Page 69
Journal Title
Breast Cancer Research
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.
Publisher
BMC
Keywords
Chromatin accessibility; Mammary gland development; Molecular heterogeneity; Progenitors; Single cell transcriptome; Terminal end bud
WEHI Research Division(s)
Cancer Biology And Stem Cells; Bioinformatics
PubMed ID
34187545
Open Access at Publisher's Site
https://doi.org/10.1186/s13058-021-01445-4
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-07-20 11:18:13
Last Modified: 2021-07-20 02:19:01
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