An integrative single-cell transcriptomic atlas of the post-natal mouse mammary gland allows discovery of new developmental trajectories in the luminal compartment.

GARCÍA SOLÁ MARTÍN; STEDILE MICAELA; BECKERMAN INÉS ; KORDON EDITH

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA

SPRINGER/PLENUM PUBLISHERS

Año: 2021

1083-3021

The mammary gland is a highly dynamic organ which undergoes periods of expansion,differentiation and cell death in each reproductive cycle. Partly because of the dynamicnature of the gland, mammary epithelial cells (MECs) are extraordinarilyheterogeneous. Single cell RNA-seq (scRNA-seq) analyses have contributed tounderstand the cellular and transcriptional heterogeneity of this complex tissue. Here,we integrate scRNA-seq data from three foundational reports that have explored themammary gland cell populations throughout development at single-cell level using 10xChromium Drop-Seq. We center our analysis on post-natal development of themammary gland, from puberty to post-involution. The new integrated studycorresponds to RNA sequences from 53,686 individual cells, which greatly outnumbersthe three initial data sets. The large volume of information provides new insights, as abetter resolution of the previously detected Procr+ stem-like cell subpopulation or theidentification of a novel group of MECs expressing immune-like markers. Moreover,here we present new pseudo-temporal trajectories of MEC populations at tworesolution levels, that is either considering all mammary cell subtypes or focusingspecifically on the luminal lineages. Interestingly, the luminal-restricted analysis revealsdistinct expression patterns of various genes that encode milk proteins, suggestingspecific and non-redundant roles for each of them. In summary, our data show that theapplication of bioinformatic tools to integrate multiple scRNA-seq data-sets helps todescribe and interpret the high level of plasticity involved in gene expression regulationthroughout mammary gland post-natal development.