Open AccessSingle-cell analysis reveals the Comma-1D cell line as a unique model for mammary gland development and breast cancer
Author(s) -
Rachel Werner,
Erin A. Nekritz,
Koon-Kiu Yan,
Bensheng Ju,
Bridget Shaner,
John Easton,
Jiyang Yu,
Jose Silva
Publication year - 2022
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.259329
Subject(s) - biology , mammary gland , cell culture , cell , microbiology and biotechnology , carcinogenesis , population , transcription factor , epithelium , mutant , cellular differentiation , cancer research , breast cancer , cancer , genetics , gene , demography , sociology
The mammary gland epithelial tree contains two distinct cell populations, luminal and basal. The investigation of how this heterogeneity is developed and how it influences tumorigenesis has been hampered by the need to perform studies on these populations using animal models. Comma-1D is an immortalized mouse mammary epithelial cell line that has unique morphogenetic properties. By performing single-cell RNA-seq studies, we found that Comma-1D cultures consist of two main populations with luminal and basal features, and a smaller population with mixed lineage and bipotent characteristics. We demonstrated that multiple transcription factors associated with the differentiation of the mammary epithelium in vivo also modulate this process in Comma-1D cultures. Additionally, we found that only cells with luminal features were able to acquire transformed characteristics after an oncogenic HER2 (also known as ERBB2) mutant was introduced in their genomes. Overall, our studies characterize, at a single-cell level, the heterogeneity of the Comma-1D cell line and illustrate how Comma-1D cells can be used as an experimental model to study both the differentiation and the transformation processes in vitro.