Transcriptional Profiling Reveals Kidney Neutrophil Heterogeneity in Both Healthy People and ccRCC Patients.
Transcriptional Profiling Reveals Kidney Neutrophil Heterogeneity in Both Healthy People and ccRCC Patients.
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转录分析揭示健康人和 ccRCC 患者的肾脏中性粒细胞异质性。
DOI：
10.1155/2021/5598627
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发表时间：
2021
影响因子：
4.1
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Meng Y;Cai K;Zhao J;Huang K;Ma X;Song J;Liu Y
已知中性粒细胞严重影响肾脏疾病的发展（例如，透明细胞肾细胞癌（ccRCC）），而ccRCC中嗜中性粒细胞的异质性仍不清楚。在本研究中，收集来自健康供体和ccRCC组织的肾活检用于单细胞RNA测序（scRNA-seq）。此外，表达并分析了健康肾脏和ccRCC肿瘤微环境（TME）中的中性粒细胞亚群。先前报道的基因被映射到这里鉴定的所有亚群。在此基础上，采用生物学主题比较法和基因集富集分析法（GSEA）对相关生物学功能进行揭示和比较。在健康的肾脏中，中性粒细胞表现出两个亚群：一个与肾脏自身免疫相关，可能作为治疗靶点;另一个被认为是抵抗感染性微生物。值得注意的是，在ccRCC活检中鉴定了六个亚群，其中两个与自身免疫更相关，而其他四个与肿瘤病理学更相关。此外，ccRCC中性粒细胞可以抵抗伊匹单抗和派姆单抗的抗癌免疫治疗，因为它们的CTLA-4、PD-1和PD-L1的低表达/无表达。因此，本研究有助于了解中性粒细胞在肾脏疾病中的异质性及其病理意义。
Neutrophil is known to critically impact the development of renal diseases (e.g., the clear cell renal cell carcinoma (ccRCC)), whereas the heterogeneity of neutrophils in ccRCC remains unclear. In the present study, kidney biopsies from healthy donors and ccRCC tissues were collected for single-cell RNA sequencing (scRNA-seq). In addition, the subpopulations of neutrophils in a healthy kidney and in the tumor microenvironment (TME) of ccRCC were expressed and then analyzed. The genes reported previously were mapped to all subpopulations identified here. On that basis, biological theme comparison and Gene Set Enrichment Analysis (GSEA) were employed to reveal and compare relevant biological functions. In a healthy kidney, neutrophils exhibit two subpopulations: one is more associated with renal autoimmunity, probably acting as therapeutic target; the other is suggested to resist infectious microorganisms. It is noteworthy that six subpopulations were identified in ccRCC biopsy, and two were more relevant to autoimmunity, while the other four are more relevant to the tumor pathology. Besides, ccRCC neutrophil could resist anticancer immune therapies of ipilimumab and pembrolizumab for their low/no expressions of CTLA-4, PD-1, and PD-L1. Thus, this study can help understand the heterogeneity and pathological significance of neutrophils in renal diseases.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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