Kaile Wang | PubMed Health

PubMed2025

Coalescing single-cell genomes and transcriptomes to decode breast cancer progression.

Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin. In contrast to bulk studies, wellDR-seq enabled the study of subclone-level gene-dosage relationships, which showed near-linear correlations in large chromosomal segments and extensive variation at the single-gene level. We identified dosage-sensitive and dosage-insensitive genes, including many breast cancer genes as well as sporadic copy-number aberrations in non-cancer cells. Overall, these data reveal complex relationships between copy number and gene expression in single cells, improving our understanding of breast cancer progression.

Breast Neoplasms↗

PubMed2024

Bioinformatics analysis of ferroptosis in frozen shoulder.

OBJECTIVES: Frozen shoulder is a common shoulder disease that significantly affects the patient's life and work. Ferroptosis is a new type of programmed cell death, which is involved in many diseases. However, there have been no studies reporting the relationship between frozen shoulders and ferroptosis. This study identified potential molecular markers of ferroptosis in frozen shoulders to provide more effective strategies for the treatment of frozen shoulders. METHODS: GSE238053 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes to obtain differentially expressed genes (DEGs). The signaling pathways and biological functions of DEGs were performed by WebGestalt and Metascape. The interactions related to these DEGs and the key genes between frozen shoulders and ferroptosis was performed by STRING and Cytoscape. A frozen shoulders rat model was used to validate our predicted genes, Western Blot and qRT-PCR was used to assess the expression levels of our genes of interest. RESULTS: A total of 34 DEGs between GSE238053 and Ferroptosis Database were obtained, most of which were involved in the HIF-1 signaling pathway and inflammatory response. A protein-protein interaction network was obtained by Cytoscape and the key genes (IL-6, HMOX1 and TLR4) were screened by MCODE. Our results of Western Blot showed that the protein expression level of TLR4 and HMOX1 were elevated, and the protein level of IL-6 decreased in frozen shoulders rat model. The mRNA level after frozen shoulders showed that IL-6 was upregulated, whereas TLR4 and HMOX1were downregulated. CONCLUSIONS: The results demonstrated that ferroptosis may affect the pathological process of frozen shoulders through these signaling pathways and genes. The identification of IL-6, HMOX1 and TLR4 genes can provide new therapeutic targets for frozen shoulders.

Ferroptosis↗