Diversity and intratumoral heterogeneity in human gallbladder cancer progression revealed by single-cell RNA sequencing.
Diversity and intratumoral heterogeneity in human gallbladder cancer progression revealed by single-cell RNA sequencing.
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单细胞 RNA 测序揭示人胆囊癌进展的多样性和瘤内异质性
DOI：
10.1002/ctm2.462
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发表时间：
2021-06
影响因子：
10.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Chen P;Wang Y;Li J;Bo X;Wang J;Nan L;Wang C;Ba Q;Liu H;Wang H
胆囊癌（GC）是一种细胞高度异质性和预后不良的恶性疾病。确定肿瘤内异质性和微环境（TME）可以为GC提供新的治疗策略。我们对5名患者的原发性和淋巴结转移性胆囊肿瘤以及邻近正常组织进行了单细胞RNA测序。对单细胞的转录组图谱和基于配体-受体的细胞间通讯网络进行了表征。获得了24，887个单细胞的转录物组景观，并表征为10个细胞簇，包括上皮细胞、神经内分泌肿瘤细胞、T&NK细胞、B细胞、RGS 5+成纤维细胞、P013+成纤维细胞、PDGFRA+成纤维细胞、内皮细胞、骨髓细胞和肥大细胞。不同类型的胃癌具有不同的上皮肿瘤亚群，鳞状细胞癌可与腺癌细胞相鉴别。腺癌和鳞癌中免疫细胞浸润丰富，而神经内分泌肿瘤中免疫细胞浸润较少，表现为间质细胞明显富集。在GC组织中鉴定出具有较高耗尽生物标志物的CD 4 +/FOXP 3 + T-reg和CD 4 +/CXCL 13 + T辅助细胞，以及肿瘤相关巨噬细胞从CCL 20 hi/CD 163 lo、CCL 20 lo/CD 163 hi到APOE+的动态谱系转变，表明免疫细胞在TME中的免疫抑制和肿瘤促进状态。两种不同的内皮细胞（KDR+和ACKR 1+），这是参与血管生成和淋巴管生成，显示出显着的配体受体与原发性GC细胞和巨噬细胞在胆囊肿瘤中的相互作用。这项研究揭示了GC进展中多个细胞群体的广泛重编程，剖析了胆囊TME中的细胞异质性和相互作用，并为GC提供了潜在的治疗靶点。腺癌和鳞癌免疫细胞丰富，神经内分泌肿瘤间质细胞富集。免疫抑制微环境特征为耗竭的T细胞和APOE+巨噬细胞。内皮细胞（KDR+和ACKR 1+）表明GC中涉及血管生成和淋巴管生成。内皮细胞、原代GC细胞和巨噬细胞之间存在显著的配体-受体相互作用。
Gallbladder cancer (GC) is a malignant disease characterized with highly cellular heterogeneity and poor prognosis. Determining the intratumoral heterogeneity and microenvironment (TME) can provide novel therapeutic strategies for GC. We performed the single‐cell RNA sequencing on the primary and lymph node metastatic gallbladder tumors and the adjacent normal tissues of five patients. The transcriptomic atlas and ligand–receptor‐based intercellular communication networks of the single cells were characterized. The transcriptomic landscape of 24,887 single cells was obtained and characterized as 10 cellular clusters, including epithelial, neuroendocrine tumor cells, T&NK cells, B cells, RGS5+ fibroblasts, POSTN+ fibroblasts, PDGFRA+ fibroblasts, endothelial, myeloid cells, and mast cells. Different types of GC harbored distinct epithelial tumor subpopulations, and squamous cell carcinoma could be differentiated from adenocarcinoma cells. Abundant immune cells infiltrated into adenocarcinoma and squamous cell carcinoma, rather than neuroendocrine neoplasms, which showed significant enrichment of stromal cells. CD4+/FOXP3+ T‐reg and CD4+/CXCL13+ T helper cells with higher exhausting biomarkers, as well as a dynamic lineage transition of tumor‐associated macrophages from CCL20hi/CD163lo, CCL20lo/CD163hi to APOE+, were identified in GC tissues, suggesting the immunosuppressive and tumor‐promoting status of immune cells in TME. Two distinct endothelial cells (KDR+ and ACKR1+), which were involved in angiogenesis and lymphangiogenesis, showed remarkable ligand–receptor interactions with primary GC cells and macrophages in gallbladder tumors. This study reveals a widespread reprogramming across multiple cell populations in GC progression, dissects the cellular heterogeneity and interactions in gallbladder TME, and provides potential therapeutic targets for GC. Abundant immune cells in adenocarcinoma and squamous cell carcinoma while stromal cells in neuroendocrine neoplasms were enriched. Immunosuppressive microenvironment characterized as exhausted T cells and APOE+ macrophages. Endothelial cells (KDR+ and ACKR1+) indicated that angiogenesis and lymphangiogenesis were involved in GC. There were remarkable ligand–receptor interactions between endothelial, primary GC cells, and macrophages.
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影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
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影响因子：
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
7.2
作者：
Hagn M;Jahrsdörfer B
通讯作者：
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影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya