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single-cell profiling of the copy-number heterogeneity in colorectal cancer

Chinese Medical Journal 2023年第6期136卷 707-718页

作者： Shiyu Song Lin Feng Kexing Xi Zhigang Sun Deyang Kong Zhenkai Luo Wei Pei Haizeng Zhang Department of Colorectal Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Lab of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:With functionally heterogeneous cells,tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment.Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth,invasion,and immune evasion.However,no reliable method to classify tumor cell subtypes is yet available.In this study,we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable(MSS)colorectal cancer(CRC).Methods:To characterize the somatic copy number alteration(SCNA)of MSS CRC in a single cell profile,we analyzed 26 tissue samples from 19 Korean patients(GSE132465,the Samsung Medical Center[SMC]dataset)and then verified our findings with 15 tissue samples from five Belgian patients(GSE144735,the Katholieke Universiteit Leuven 3[KUL3]dataset).The Cancer Genome Atlas(TCGA)cohort,GSE39582 cohort,and National Cancer Center(NCC)cohort(24 MSS CRC patients were enrolled in this study between March 2017 and October 2017)were used to validate the clinical features of prognostic signatures.Results:We employed single cell rna-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics.Among these three types of tumor cells,C1 and C3 had a higher SCNA burden;C1 had significant chromosome 13 and 20 amplification,whereas C3 was the polar opposite of C1,which exhibited deletion in chromosome 13 and 20.The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations.C1 and C2 were linked to the immune response and hypoxia,respectively,while C3 was critical for cell adhesion activity and tumor angiogenesis.Additionally,one gene(OLFM4)was identified as epithelium-specific biomarker of better prognosis of CRC(TCGA cohort:P=0.0110;GSE39582 cohort:P=0.0098;NCC cohort:P=0.0360).Conclusions:On the basis of copy number characteristics,we illustrated tumor heterogeneity in MSS CRC and iden

关键词： Somatic copy number alteration Microsatellite stable Colorectal cancer single cell rna-sequencing Intra-tumor genetic heterogeneity

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Application of single-cell omics in inflammatory bowel disease

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World Journal of Gastroenterology 2023年第28期29卷 4397-4404页

作者： Hengqi Betty Zheng Department of Pediatrics Seattle Children’s HospitalUniversity of WashingtonSeattleWA 98105United States

Over the past decade,the advent of single cell rna-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.single-cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as single-cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through single-cell omics can change our approach to translational research.As novel techniques evolve through multiplexing single-cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.

关键词： single-cell omics Inflammatory bowel disease Crohn’s disease Ulcerative colitis single cell rna-sequencing Precision medicine

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