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Single-Cell RNA-Seq Reveals Heterogeneous lncRNA Expression in Xenografted Triple-Negative Breast Cancer Cells
Holly R Pinkney1, Michael A Black1, Sarah D Diermeier1,2
1Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand.
Biology
|October 23, 2021
Summary
Investigating long non-coding RNAs (lncRNAs) in triple-negative breast cancer (TNBC) reveals heterogeneous expression patterns. LncRNA expression alone cannot define TNBC cell subpopulations, highlighting complexity in tumor heterogeneity.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Triple-negative breast cancer (TNBC) is a highly heterogeneous malignancy, posing challenges for treatment.
- Tumor heterogeneity involves varying gene expression profiles and aggressive subclonal populations.
- Long non-coding RNAs (lncRNAs) are increasingly recognized as regulatory molecules in cancer.
Purpose of the Study:
- To investigate in vivo TNBC tumor heterogeneity at the single-cell level.
- To determine if lncRNA expression varies across individual cells within TNBC tumors.
- To assess if lncRNA expression is sufficient to define distinct cellular subpopulations.
Main Methods:
- Application of single-cell RNA sequencing (scRNA-seq) to profile lncRNA expression.
- Analysis of lncRNA expression in TNBC xenografts at single-cell resolution.
- Characterization of lncRNA expression patterns, including ubiquitous, subpopulation-specific, and hybrid expression.
Main Results:
- Most lncRNAs were detected at low levels in TNBC xenografts, with a median of 25 lncRNAs per cell.
- lncRNA expression alone was insufficient to define distinct cellular subpopulations.
- Observed heterogeneous lncRNA expression patterns across cells and subpopulations.
Conclusions:
- Transcriptionally defined tumor cell subpopulations can be identified in cell-line derived xenografts.
- lncRNA expression is highly heterogeneous within TNBC tumors.
- Further research is needed to explore lncRNAs as potential therapeutic targets and biomarkers for TNBC.

