ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Breast Cancer Res. 2021 Jun 29;23(1):69. doi: 10.1186/s13058-021-01445-4.
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.
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.
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.
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.
最近通过单细胞 RNA 分析探索了小鼠乳腺上皮细胞的异质性和潜在的谱系关系。为了进一步了解细胞多样性在乳腺发生过程中如何变化，我们对九个不同发育阶段的单个细胞进行了分析，这些阶段跨越了胚胎后期、出生后早期、青春期前、成年期、妊娠中期、妊娠晚期和退化后，以及青春期时的末端芽（TEB）和下伏导管的微切割的转录组。
在 10x Genomics Chromium 平台上测定了来自 9 个不同发育阶段的 132599 个乳腺上皮细胞的单细胞转录组，并进行了综合分析以比较特定的时间点。
E18.5 的乳腺原基与基底谱系密切相关，而青春期前的上皮细胞表现出谱系分离，但分化程度低于成年细胞。比较微切割的 TEB 与导管显示，TEB 内的腔细胞具有中间表达谱。与 TEB 相比，导管基底细胞表现出更高的腔基因染色质可及性，这表明在青春期，亚基导管内建立了谱系特异性染色质。对跨越妊娠周期的五个阶段的综合分析显示出独特的阶段特异性特征，并在妊娠期间存在循环基底、混合谱系和“晚期”肺泡中间细胞。此外，沿着基底-腔前体细胞轴发现了许多中间细胞，这表明肺泡限制前体细胞状态具有连续性。
该小鼠乳腺上皮细胞的扩展单细胞转录组图谱提供了迄今为止乳腺上皮细胞在形态发生过程中最完整的覆盖。与 TEB 结构的染色质可及性分析一起，它代表了理解小鼠乳腺内发育决策的有价值框架。
