Dynamic heterogeneity of colorectal cancer during progression revealed clinical risk-associated cell types and regulations in single-cell resolution and spatial context

作     者：Haoxian Ke Zhihao Li Peisi Li Shubiao Ye Junfeng Huang Tuo Hu Chi Zhang Ming Yuan Yuan Chen Xianrui Wu Ping Lan 

作者机构：Department of General Surgery(Colorectal Surgery)The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesGuangdong Institute of GastroenterologyThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China School of MedicineSun Yat-sen UniversityShenzhenGuangdongP.R.China 

出 版 物：《Gastroenterology Report》 (胃肠病学报道（英文）)

年 卷 期：2023年第11卷第1期

页      面：365-384页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China[grant number 2022YFA1304000] the National Natural Science Foundation of China Key Joint Project[grant number U21A20344] the National Natural Science Foundation of China[grant number 81970452] the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases[grant number 2020B1111170004] the Science and Technology Program of Shenzhen,China[grant number JCYJ20190807161807867] the Starting Funding of Faculty from Sun Yat-sen University[grant number 2021276] the Regional Joint Project for Basic and Applied Basic Research Fund of Guangdong Province[grant number 2022A1515111043] the Science and Technology Planning Project of Guangzhou City[grant number 2023A04J01601],and National Key Clinical Discipline 

主　　题：colorectal cancer tumor heterogeneity tumor progression single-cell RNA sequencing spatial transcription sequencing 

摘      要：Background:Tumor heterogeneity is contributed by tumor cells and the *** of tumor heterogeneity during colorectal cancer(CRC)progression have not been ***:Eight single-cell RNA sequencing(scRNA-seq)data sets of CRC were *** was utilized to reveal the differential abundance of cell clusters during *** differentiation trajectory was imputed by using the Palantir algorithm and metabolic states were assessed by using *** spatial transcription sequencing(ST-seq)data sets of CRC were used to validate cell-type abundances and ***-associated regulatory hubs were defined as communication networks affecting tumor biological ***,quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining were performed for ***:TM4SF1t,SOX4t,and MKI67t tumor cells;CXCL12t cancer-associated fibroblasts;CD4t resident memory T cells;Treg;IgAt plasma cells;and several myeloid subsets were enriched in stage IV CRC,most of which were associated with overall survival of *** analysis indicated that tumor cells from patients with advanced-stage CRC were less differentiated,when metabolic heterogeneity showed a highest metabolic signature in terminal states of stromal cells,T cells,and myeloid ***,ST-seq validated cell-type abundance in a spatial context and also revealed the correlation of immune infiltration between tertiary lymphoid structures and tumors followed by validation in our ***,analysis of cancer-associated regulatory hubs revealed a cascade of activated pathways including leukocyte apoptotic process,MAPK pathway,myeloid leukocyte differentiation,and angiogenesis during CRC ***:Tumor heterogeneity was dynamic during progression,with the enrichment of immunosuppressive Treg,myeloid cells,and fibrotic *** differential state of tumor cells was associated with cancer staging.