A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis.
A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis.
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DOI：
10.20517/2394-4722.2019.24
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Keri, Ruth
中科院分区：
文献类型：
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作者：
Anstine, Lindsey J;Keri, Ruth
乳腺上皮干细胞（MaSC）群体能够介导乳腺发育和稳态的存在已经建立了十多年。谱系追踪和乳腺移植研究的组合已经证实MaSC及其下游祖细胞以分层方式组织;然而，这些技术未能阐明上皮中间群体的完整谱或其空间和时间关系。单细胞测序技术的出现允许以高分辨率表征高度异质性组织。在过去的两年中，单细胞RNA测序（scRNA-seq）技术的显着进步已被用于解决乳腺上皮的异质性。这些研究提供了新的见解，转录分化的层次和它的年表。重要的是，这些数据导致了一个重大的概念转变，其中分离干细胞，祖细胞和分化的上皮细胞群的刚性边界已被解构，从而产生了一个新的更具流动性和灵活性的上皮细胞分化模型。新出现的乳腺上皮层次结构的观点对乳腺发育，癌变和转移具有重要意义，为可能促进恶性表型的潜在细胞状态提供了新的见解。
The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland development and homeostasis has been established for over a decade. A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner; however, these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships. The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution. In the last two years, the remarkable advances in single cell RNA sequencing (scRNA-seq) technologies have been leveraged to address the heterogeneity of the mammary epithelium. These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology. Importantly, these data have led to a major conceptual shift in which the rigid boundaries separating stem, progenitor, and differentiated epithelial populations have been deconstructed, resulting in a new more fluid and flexible model of epithelial differentiation. The emerging view of the mammary epithelial hierarchy has important implications for mammary development, carcinogenesis, and metastasis, providing novel insights into the underlying cellular states that may promote malignant phenotypes.