Single cell transcriptome sequencing of mammary stem cells in the pubertal mammary gland

The mammary gland is a highly dynamic organ that mainly develops during puberty. Based on morphology and proliferation analysis, mammary stem cells (MaSCs) are thought to be close to or reside in the terminal end buds (TEBs) during pubertal development. However, exclusive stem cell markers are lacking, and therefore the true identity of MaSCs, including their location, multiplicity, dynamics and fate during branching morphogenesis, has yet to be defined. To gain more insights into the molecular identity and heterogeneity of the MaSC pool, we performed single cell transcriptome sequencing of mammary epithelial cells micro-dissected from ducts and TEBs during puberty. These data show that the behaviour of MaSCs cannot be directly linked to a single expression profile. Instead, morphogenesis of the mammary epithelium relies upon a heterogeneous population of MaSCs that functions long-term as a single equipotent pool of stem cells.

乳腺是一类高度动态的器官，其发育主要发生于青春期阶段。基于形态学与增殖分析，学界普遍认为青春期发育过程中，乳腺干细胞（mammary stem cells, MaSCs）贴近或定居于末端芽体（terminal end buds, TEBs）。然而目前尚缺乏特异性的干细胞标志物，因此乳腺干细胞的真实特性——包括其在分支形态发生过程中的定位、多态性、动态变化与细胞命运——仍有待明确。为深入解析乳腺干细胞群体的分子特性与异质性，我们对青春期阶段从导管与末端芽体（TEBs）中显微切割获取的乳腺上皮细胞开展了单细胞转录组测序。分析数据表明，乳腺干细胞的行为无法与单一的表达谱直接关联；相反，乳腺上皮的形态发生依赖于一个异质性的乳腺干细胞群体，该群体作为一个统一的等能干细胞池长期发挥功能。