Analysis of Transcription Factors in Breast Cancer Epithelial Cells Based on Single-cell ATAC-seq Data

ZHANG Yana, MOU Yuanjing, LI Weixiang, ZHAO Junyan, GUO Zhiyun

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Life Science Research ›› 2024, Vol. 28 ›› Issue (2) : 171-178.

Analysis of Transcription Factors in Breast Cancer Epithelial Cells Based on Single-cell ATAC-seq Data

  • ZHANG Yana, MOU Yuanjing, LI Weixiang, ZHAO Junyan, GUO Zhiyun
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Abstract

Studies have shown that transcription factors binding to open chromatin regions in breast tumor cells significantly influence the clinical phenotype and prognosis of breast cancer patients. However, it is unclear how these regulatory elements regulate the occurrence and development of breast cancer at the sin-gle-cell level. Herein, single-cell chromatin accessibility sequencing (single-cell ATAC sequencing, scATAC-seq) data of 45 216 normal and tumor breast tissues were downloaded from the GEO database, and seven breast cell types were obtained after cell type annotation based on gene activity scores of marker genes in cell populations. Pearson correlation analysis showed significant differences in chromatin accessibility be-tween tumor and normal breast epithelial cells, and a high degree of inter-sample heterogeneity of breast epithelial cells (PCC=-0.07), implying that they are the main malignant cell type in breast tumors. To explore the enrichment of transcription factor motifs in the differentially accessible regions of normal and malignant mammary epithelial cells, motif enrichment analysis was performed on the characteristic open regions of the four epithelial cell subtypes after extraction of the epithelial cell populations. The results showed that malig-nant breast epithelial cells were significantly enriched for 194 transcription factors (P<0.001), which may be involved in regulatory processes of breast tumor development and metastasis. Calculation of activity scores and validation of transcriptome data for transcription factors highly enriched in epithelial cell subtypes fur-ther showed that these differential regulatory elements may be associated with malignant development of breast cells. In addition, differences in the accessibility of transcription factor binding motifs in different breast can-cer subtypes were analyzed, and SNAI2 was found to have significantly high accessibility in triple-negative breast cancer samples, suggesting that SNAI2 has a potential specific regulatory role in triple-negative breast cancer.

Key words

breast carcinoma / single nucleated cell / single-cell ATAC sequencing (scATAC-seq) / transcrip-tion factor

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ZHANG Yana, MOU Yuanjing, LI Weixiang, ZHAO Junyan, GUO Zhiyun. Analysis of Transcription Factors in Breast Cancer Epithelial Cells Based on Single-cell ATAC-seq Data. Life Science Research. 2024, 28(2): 171-178

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