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Single-cell RNA sequencing (scRNA-seq) provides molecular, cellular, and immunological resolution to study TME composition, transcriptional dynamics, and intratumor heterogeneity. 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[https://doi.org/10.1007/s00262-024-03820-4](https://doi.org/10.1007/s00262-024-03820-4)  \nSingle‑cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy  \nJiao Xu1 · Bixin Yu2 · Fan Wang3 · Jin Yang1,2,3,4  \nReceived: 23 July 2024 / Accepted: 27 August 2024 / Published online: 13 September 2024 © The Author(s) 2024  \nAbstract  \nGastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.  \nKeywords Gastric cancer · Tumor microenvironment · Immune cell · Single-cell RNA sequencing · Spatial transcriptomes  \nAbbreviations  \nACRG Asian Cancer Research Group  \nAPB Alternate promoter burden  \nAR Androgen receptor  \n* Fan Wang [wangfan230@outlook.com](wangfan230@outlook.com)  \n* Jin Yang [yangjin@xjtu.edu.cn](yangjin@xjtu.edu.cn)  \n1 Precision Medicine Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road., Xi’an 710061, Shaanxi, People’s Republic of China  \n2 Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road., Xi’an 710061, Shaanxi, People’s Republic of China  \n3 Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China  \n4 Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China  \nCAF  \nCAFEndMT  \nCAG  \nCSC  \nCTC  \nCTLA-4  \nCTShigh CXCL  \nCXCRC1Qhigh DC  \nDGC  \nDIC  \nDZIP1  \nEBV  \neCAF  \nECM  \nEMT  \nGC  \nCancer-associated fibroblast Endothelial-to-mesenchymal transition CAF  \nChronic atrophic gastritis Cancer stem cell Circulating tumor cell  \nCytotoxic T-lymphocyte-associated antigen 4  \nCathepsinhigh  \nC-X-C motif chemokine ligand  \nC-X-C motif chemokine receptor  \nComplement 1qhigh Dendritic cell Diffuse-type GC  \nDisseminated intravascular coagulation DAZ interacting zinc finger protein 1 Epstein-Barr virus  \nExtracellular matrix CAF  \nExtracellular matrix  \nEpithelial-to-mesenchymal transition Gastric cancer  \nGI  \nGITR  \nGkn3  \nGR  \nGSRCC  \nHAGC  \nICI  \nICBiCAFIFN-γ ILILC2  \nIM  \nITH  \nIGCISG15  \nLM  \nLAG3  \nLNM  \nMDSC  \nMALT  \nMALAT1  \nMSI MSI-high NACT NK cell PM PBMC PDGFRβ POSTNPD-L1  \nPD-1  \nPDX scATAC-seq  \nscBCR-seq  \nscRNA-seq  \nscTCR-seq  \nscCHIP-seq SPEM  \nSL  \nSM  \nST  \nTAN  \nTAM  \nTex  \nTCGA  \nTIB  \nTIGIT  \nTLS  \nGastrointestinal cancer  \nGl","cbCaimgPmVePBOWj","https://ap.wps.com/l/cbCaimgPmVePBOWj","pdf",1065295,16,"English","# Abstract\n# Keywords\n## Abbreviations","[{\"question\":\"What problem does the article address about gastric cancer?\",\"answer\":\"It focuses on gastric cancer as a highly heterogeneous disease with a complex tumor microenvironment (TME) that influences progression and therapeutic response.\"},{\"question\":\"How does single-cell RNA sequencing contribute to studying gastric carcinogenesis?\",\"answer\":\"scRNA-seq reveals the origin and evolution of gastric cancer from single-cell datasets and enables analysis of transcriptional dynamics and intratumor heterogeneity.\"},{\"question\":\"Which cell types and technologies are emphasized for understanding the TME and therapy?\",\"answer\":\"Key immune cells such as T cells, B cells, macrophages, and stromal cells are highlighted, and spatial transcriptomes are discussed for determining spatial distribution and local intercellular communication networks.\"}]","Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy | PDF",1789998354]