Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones

Cao, Wei1,2; Wang, Xuefei1; Luo, Kaiwen1; Li, Yang3; Sun, Jiahong1; Fu, Ruqing1; Zhang, Qi1; Hong, Ni1; Cheung, Edwin2; Jin, Wenfei4

2024-03-30

10.1016/j.heliyon.2024.e28071

HELIYON   影响因子和分区

2405-8440

To explore the feature of cancer cells and tumor subclones, we analyzed 101,065 single-cell transcriptomes from 12 colorectal cancer (CRC) patients and 92 single cell genomes from one of these patients. We found cancer cells, endothelial cells and stromal cells in tumor tissue expressed much more genes and had stronger cell-cell interactions than their counterparts in normal tissue. We identified copy number variations (CNVs) in each cancer cell and found correlation between gene copy number and expression level in cancer cells at single cell resolution. Analysis of tumor subclones inferred by CNVs showed accumulation of mutations in each tumor subclone along lineage trajectories. We found differentially expressed genes (DEGs) between tumor subclones had two populations: DEGCNV and DEGreg. DEGCNV, showing high CNVexpression correlation and whose expression differences depend on the differences of CNV level, enriched in housekeeping genes and cell adhesion associated genes. DEGreg, showing low CNV-expression correlation and mainly in low CNV variation regions and regions without CNVs, enriched in cytokine signaling genes. Furthermore, cell-cell communication analyses showed that DEGCNV tends to involve in cell-cell contact while DEGreg tends to involve in secreted signaling, which further support that DEGCNV and DEGreg are two regulatorily and functionally distinct categories.

Colorectal cancer Single cell RNA sequencing Single cell whole genome sequencing Copy number variations Differentially expressed gene Cell-cell communication

SCI

英语

第一 ; 通讯

National Key R&D Program of China[2021YFF1200900] ; National Natural Science Foundation of China["32170646","32370688"] ; Key-Area Research and Development Program of Guangdong Province[2023B1111020006] ; Guangdong Basic and Applied Basic Research Foundation[2023A1515011908] ; Shenzhen Innovation Committee of Science and Technology[JCYJ20220818100401003] ; Shenzhen Science and Technology Program[KQTD20180411143432337]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001209791200001

CELL PRESS

Web of Science

1.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen, Peoples R China
2.Univ Macau, Fac Hlth Sci, Canc Ctr, Taipa, Macau, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen, Peoples R China
4.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol, Shanghai, Peoples R China

Cao, Wei,Wang, Xuefei,Luo, Kaiwen,et al. Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones[J]. HELIYON,2024,10(6).

Cao, Wei.,Wang, Xuefei.,Luo, Kaiwen.,Li, Yang.,Sun, Jiahong.,...&Jin, Wenfei.(2024).Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones.HELIYON,10(6).

Cao, Wei,et al."Single cell analyses of cancer cells identified two regulatorily and functionally distinct categories in differentially expressed genes among tumor subclones".HELIYON 10.6(2024).