Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing.
Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing.
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DOI：
10.1038/s41467-017-02001-5
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发表时间：
2017-12-11
影响因子：
16.6
通讯作者：
Khaled WT
中科院分区：
文献类型：
--
作者：
Bach K;Pensa S;Grzelak M;Hadfield J;Adams DJ;Marioni JC;Khaled WT
表征乳腺上皮细胞(MECs)的层次结构以及它们在成人发育过程中如何受到调控，对于理解乳腺癌是如何发生的非常重要。在这里，我们报告了使用单细胞RNA测序来确定MEC在四个发育阶段：未分娩、妊娠中期、哺乳和退缩后的基因表达谱。我们对23,184个细胞的分析确定了15个簇，其中很少能完全由单个标记基因来表征。相反，我们认为上皮细胞--尤其是腔间隔内的上皮细胞--更应该被概念化为连续分化谱的一部分。此外，我们的数据支持共同的腔前体细胞的存在，从而产生中间的、受限的肺泡祖细胞和激素敏感的祖细胞。在完全怀孕、哺乳和退缩的过程中，这个腔内的祖细胞亚室经历转录变化。总而言之，我们的研究结果为成人乳腺发育提供了一个全面、公正的观点。有必要了解乳腺上皮细胞如何对不同发育阶段的变化做出反应。在这里，作者使用不同成人发育阶段的乳腺上皮细胞的单细胞RNA测序，识别不同的细胞类型并绘制它们的发育轨迹。
Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells—especially in the luminal compartment—should rather be conceptualised as being part of a continuous spectrum of differentiation. Furthermore, our data support the existence of a common luminal progenitor cell giving rise to intermediate, restricted alveolar and hormone-sensing progenitors. This luminal progenitor compartment undergoes transcriptional changes in response to a full pregnancy, lactation and involution. In summary, our results provide a global, unbiased view of adult mammary gland development. There is a need to understand how mammary epithelial cells respond to changes at various developmental stages. Here, the authors use single-cell RNA sequencing of mammary epithelial cells at different adult developmental stages, identifying different cell types and charting their developmental trajectory.
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影响因子：
12.3
作者：
Lun AT;Bach K;Marioni JC
通讯作者：
Marioni JC
影响因子：
64.5
作者：
Kouros-Mehr, Hosein;Slorach, Euan M.;Werb, Zena
通讯作者：
Werb, Zena
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian
影响因子：
21.3
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
使用纳米液液滴对单个细胞的高度平行基因组表达分析。
影响因子：
64.5
作者：
Macosko EZ;Basu A;Satija R;Nemesh J;Shekhar K;Goldman M;Tirosh I;Bialas AR;Kamitaki N;Martersteck EM;Trombetta JJ;Weitz DA;Sanes JR;Shalek AK;Regev A;McCarroll SA
通讯作者：
McCarroll SA