关键词: Cystadenomas Hepatic cysts Microenvironment Single nucleus RNA-Sequencing Spatial transcriptomics sequencing

Mesh : Humans Cysts / genetics pathology Tumor Microenvironment / genetics Cystadenoma / genetics pathology Liver Neoplasms / genetics pathology metabolism Transcriptome / genetics Sequence Analysis, RNA Single-Cell Analysis / methods Liver / pathology metabolism Female Liver Diseases

来  源:   DOI:10.1016/j.compbiomed.2024.108541

Abstract:
Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.
摘要:
肝囊腺瘤是一种罕见的疾病,约占所有囊性病变的5%,恶性转化的趋势很高。囊腺瘤的术前诊断困难,有些囊腺瘤一开始容易误诊为肝囊肿。肝囊肿是一种比较常见的肝病,其中大多数是良性的,但是大的肝囊肿会导致胆管受压,导致肝功能异常。为了更好地了解囊腺瘤和肝囊肿的微环境之间的差异,我们对囊腺瘤和肝囊肿样本进行了单核RNA测序.此外,我们对肝囊肿进行了空间转录组测序。根据细胞核RNA测序数据,总共确定了七种主要细胞类型。在这里,我们描述了囊腺瘤和肝囊肿的肿瘤微环境,特别是免疫细胞和基质细胞的转录组特征和调节因子。通过推断拷贝数变化,发现囊腺瘤中肝星状细胞的恶性程度较高。假时间轨迹分析显示肝细胞在肝囊肿和囊腺瘤中的动态转化。囊腺瘤的免疫浸润高于肝囊肿,T细胞在囊腺瘤中比肝囊肿具有更复杂的调节机制。免疫组织化学证实了囊腺瘤特异性T细胞免疫调节机制。这些结果提供了囊腺瘤和肝囊肿的单细胞图谱,揭示了囊腺瘤比肝囊肿更复杂的微环境,为囊腺瘤和肝囊肿的分子机制研究提供了新的视角。
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