Integrative single-cell transcriptomic analysis unveils alternative polyadenylation modulation in the mouse mammary gland

Martin E. García Solá¹, Mercedes Montani¹, Micaela Stedile¹, Inés Beckerman¹, Omar Coso¹, Edith Kordon¹


The mammary gland (MG) is a highly dynamic organ which undergoes periods of expansion, differentiation and cell death in each reproductive cycle. Single cell RNA-seq (scRNA-seq) analyses have contributed to understand the cellular and transcriptional heterogeneity of this complex tissue. Alternative polyadenylation (APA) generates diverse mRNA isoforms, which contributes to transcriptome diversity and gene expression regulation by affecting mRNA stability, translation and intracellular localization. This study is based on publicly available data from 53,686 individual cells obtained during mammary post-natal development, from puberty to post-involution. The original data-sets correspond to three foundational reports that have explored the MG cell populations throughout development at single-cell level using 3′tag-based scRNA-seq. This feature of the sequencing protocol allowed us to analyze APA patterns in the mammary epithelial cells (MECs). Our results show relevant changes in gene families associated with mRNA processing, such as hnRNP, Eif and Srsf, in different mammary cell linages throughout the post-natal phases. Besides, APA modulation is also observed in key mRNAs for MG development and function, as Egfr1 and Prlr., which encode EGF receptor and Prolactin receptor, respectively In summary, this study reveals that APA may provide a new control layer on gene expression regulation in MECs throughout puberty and adulthood.