Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

Liu, Yang; He, Shuai; Wang, Xiliang; Wan, Peng; Chen, Qiuyan; Chi, Dongmei; Chen, Jierong; Han, Bo‐Wei; Lin, Guo‐Wang; Li, Yiqi; Wang, Qianyu; Peng, Roujun; Wei, Panpan; Guo, Xiang; Li, Bo; Xia, Xiaojun; Mai, Hai-Qiang; Hu, Xueda; Zhang, Zemin; Zeng, Yi-Xin; Bei, Jin‐Xin

doi:10.1038/s41467-021-21043-4

Cited by 138 publications

(191 citation statements)

References 78 publications

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“…cDCs expressing the SOCS2-centralized gene program could facilitate tumor immune surveillance ( 114 ). Clusters of IDO1 + cDCs and LAMP3 + cDCs are reported to repress the proliferation and function of effector T cells ( 115 , 116 ). DCs could also be restrained by regulatory T cells ( 117 ).…”

Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 99%

“…In addition, a cluster of IDO1 + cDCs was identified in tumor environments and was predicted to impair T cell proliferation and cytotoxicity by promoting tryptophan depletion and kynurenine production ( 115 ). Interestingly, a cluster of tolerogenic and regulatory DCs, highly expressing migration (CCR7)- and maturation (LAMP3)-related genes, along with various chemokine ligands (CCL17, CCL19, and CCL22), was presumably able to interact with regulatory T cells and exhausted CD8 + T cells by binding to corresponding receptors in nasopharyngeal carcinoma at single-cell resolution ( 116 ). This immune-suppressive transcriptomic pattern in LAMP3 + DCs has been widely detected in various tumors by scRNA-seq, including in bladder urothelial carcinoma ( 128 ), hepatocellular carcinoma ( 129 , 130 ), and lung cancer ( 119 , 131 ), suggesting that universal crosstalk fosters an immune-suppressive niche for the tumor microenvironment.…”

Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 99%

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Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

et al. 2021

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Dendritic cells (DCs) play essential roles in innate and adaptive immunity and show high heterogeneity and intricate ontogeny. Advances in high-throughput sequencing technologies, particularly single-cell RNA sequencing (scRNA-seq), have improved the understanding of DC subsets. In this review, we discuss in detail the remarkable perspectives in DC reclassification and ontogeny as revealed by scRNA-seq. Moreover, the heterogeneity and multifunction of DCs during diseases as determined by scRNA-seq are described. Finally, we provide insights into the challenges and future trends in scRNA-seq technologies and DC research.

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Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 99%

Section: Applications Of Scrna-seq In DC Studiesmentioning

confidence: 99%

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

et al. 2021

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“…We reasoned that this bioinformatics challenge is theoretically possible with the EBV γ-herpesvirus genome given that it has been demonstrated for α-and β-herpesviruses [35][36][37]. Recent reports have demonstrated that scRNAseq alignment to EBV is possible in EBV-infected lymphoblastoid cell lines and NPC tumors [38][39][40], although alignment spanning the EBV genome has yet to be demonstrated. This is more likely to be observed in lytic-infected cells such as those in pseudo-ALI culture.…”

Section: Single Cell Rna-sequencing Reveals Cell Type-specific Ebv Transcriptional Profilesmentioning

confidence: 99%

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection

et al. 2021

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Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

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“…Five subclusters of cells were identified from the GCTB lesion: C1_CD8 + T cells, C2_T cells, C3_T cells, C4_NK cells and C5_ CD8 + T cells ( Figures 5A, B ). C1_CD8 + T cells, and C2_CD8 + T cells shared specific T-cell markers genes, such as CD3D, CD3E, CD3G, CD8A, and CD8B ( 19 , 45 ). C2_T cells and C3_T cells expressed CD3D, CD3E, and CD3G.…”

Section: Resultsmentioning

confidence: 99%

“…Multiplex immunohistochemistry staining was performed according to the manufacturer’s instructions using the PANO 7-plex IHC kit (Panovue, Beijing, China) ( 19 , 20 ). Sections with a thickness of 3 μm were incubated overnight at 4°C with primary antibodies: anti-ACP5 (cat.…”

Section: Methodsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

Feng

Jiang

et al. 2021

Front. Oncol.

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Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

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Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

Cited by 138 publications

References 78 publications

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

Unraveling the Heterogeneity and Ontogeny of Dendritic Cells Using Single-Cell RNA Sequencing

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

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