Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland

Henry, Samantha, Trousdell, Marygrace C, Cyrill, Samantha L, Zhao, Yixin, Feigman, Mary J, Bouhuis, Julia M, Aylard, Dominik A, Siepel, Adam, Dos Santos, Camila O (May 2021) Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland. Journal of Mammary Gland Biology and Neoplasia. ISSN 1083-3021

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Abstract

The developing mammary gland depends on several transcription-dependent networks to define cellular identities and differentiation trajectories. Recent technological advancements that allow for single-cell profiling of gene expression have provided an initial picture into the epithelial cellular heterogeneity across the diverse stages of gland maturation. Still, a deeper dive into expanded molecular signatures would improve our understanding of the diversity of mammary epithelial and non-epithelial cellular populations across different tissue developmental stages, mouse strains and mammalian species. Here, we combined differential mammary gland fractionation approaches and transcriptional profiles obtained from FACS-isolated mammary cells to improve our definitions of mammary-resident, cellular identities at the single-cell level. Our approach yielded a series of expression signatures that illustrate the heterogeneity of mammary epithelial cells, specifically those of the luminal fate, and uncovered transcriptional changes to their lineage-defined, cellular states that are induced during gland development. Our analysis also provided molecular signatures that identified non-epithelial mammary cells, including adipocytes, fibroblasts and rare immune cells. Lastly, we extended our study to elucidate expression signatures of human, breast-resident cells, a strategy that allowed for the cross-species comparison of mammary epithelial identities. Collectively, our approach improved the existing signatures of normal mammary epithelial cells, as well as elucidated the diversity of non-epithelial cells in murine and human breast tissue. Our study provides a useful resource for future studies that use single-cell molecular profiling strategies to understand normal and malignant breast development.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression organism description > animal > mammal > primates > hominids > human organs, tissues, organelles, cell types and functions > tissues types and functions > mammary gland organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Trousdell, Marygrace C Cyrill, Samantha L Zhao, Yixin Feigman, Mary J. Siepel, Adam Dos Santos, Camila O. Henry, Samantha
Communities:	CSHL labs > Dos Santos lab CSHL labs > Siepel lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service CSHL Cancer Center Shared Resources > Single-Cell Biology Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	14 May 2021
Date Deposited:	19 May 2021 17:31
Last Modified:	13 Feb 2024 16:59
PMCID:	PMC8217035
URI:	https://repository.cshl.edu/id/eprint/40090

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