Single-Cell Transcriptomes Distinguish Stem Cell State Changes and Lineage Specification Programs in Early Mammary Gland Development

单细胞转录组学揭示早期乳腺发育过程中干细胞状态的变化和谱系分化程序

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作者:Rajshekhar R Giraddi ,Chi-Yeh Chung ,Richard E Heinz ,Ozlen Balcioglu ,Mark Novotny ,Christy L Trejo ,Christopher Dravis ,Berhane M Hagos ,Elnaz Mirzaei Mehrabad ,Luo Wei Rodewald ,Jae Y Hwang ,Cheng Fan ,Roger Lasken ,Katherine E Varley ,Charles M Perou ,Geoffrey M Wahl ,Benjamin T Spike

Abstract

The mammary gland consists of cells with gene expression patterns reflecting their cellular origins, function, and spatiotemporal context. However, knowledge of developmental kinetics and mechanisms of lineage specification is lacking. We address this significant knowledge gap by generating a single-cell transcriptome atlas encompassing embryonic, postnatal, and adult mouse mammary development. From these data, we map the chronology of transcriptionally and epigenetically distinct cell states and distinguish fetal mammary stem cells (fMaSCs) from their precursors and progeny. fMaSCs show balanced co-expression of factors associated with discrete adult lineages and a metabolic gene signature that subsides during maturation but reemerges in some human breast cancers and metastases. These data provide a useful resource for illuminating mammary cell heterogeneity, the kinetics of differentiation, and developmental correlates of tumorigenesis.

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