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Updated: Aug 8, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
The Breast Cancer Single-Cell Atlas: Defining cellular heterogeneity within model cell lines and primary tumors to
Arpit Dave1, Daniel Charytonowicz1, Nancy J Francoeur1,2
1Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave - Icahn (East) Building, Floor 14, Room 14-20E, New York, NY, 10029, USA.
Purpose:
Breast Cancer (BC) is the most diagnosed cancer in women; however, through significant research, relative survival rates have significantly improved. Despite progress, there remains a gap in our understanding of BC subtypes and personalized treatments. This manuscript characterized cellular heterogeneity in BC cell lines through scRNAseq to resolve variability in subtyping, disease modeling potential, and therapeutic targeting predictions.
Methods:
We generated a Breast Cancer Single-Cell Cell Line Atlas (BSCLA) to help inform future BC research. We sequenced over 36,195 cells composed of 13 cell lines spanning the spectrum of clinical BC subtypes and leveraged publicly available data comprising 39,214 cells from 26 primary tumors.
Results:
Unsupervised clustering identified 49 subpopulations within the cell line dataset. We resolve ambiguity in subtype annotation comparing expression of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 genes. Gene correlations with disease subtype highlighted S100A7 and MUCL1 overexpression in HER2 + cells as possible cell motility and localization drivers. We also present genes driving populational drifts to generate novel gene vectors characterizing each subpopulation. A global Cancer Stem Cell (CSC) scoring vector was used to identify stemness potential for subpopulations and model multi-potency. Finally, we overlay the BSCLA dataset with FDA-approved targets to identify to predict the efficacy of subpopulation-specific therapies.
Conclusion:
The BSCLA defines the heterogeneity within BC cell lines, enhancing our overall understanding of BC cellular diversity to guide future BC research, including model cell line selection, unintended sample source effects, stemness factors between cell lines, and cell type-specific treatment response.
