Therapy resistance in prostate cancer arises from coordinated remodeling of malignant and stromal compartments, yet the mechanisms orchestrating this ecosystem adaptation remain elusive. Here, single-cell RNA sequencing of longitudinal biopsies obtained before and after androgen-deprivation therapy (ADT) delineated a therapy-induced stromal lineage bifurcation toward APOD+ and DPT+ fibroblast states. DPT+ fibroblasts activated a C3-ITGAX/ITGB2 complement signaling axis targeting macrophages, coinciding with suppression of M1 inflammatory programs, amplification of immune-checkpoint signaling, and a shift of CD8+ T cells from cytotoxic to exhausted phenotypes. Concomitantly, we identified pre-existing malignant epithelial subpopulations characterized by reduced AR/KLK3 activity and heightened chromosomal instability that preferentially persisted following therapy. Integrative multi-omic analyses nominated TSPAN1 as a functional effector of castrate resistant prostate cancer (CRPC) and NRXN1 as a regulator of neuroendocrine plasticity through calcium-dependent signaling programs. Genetic silencing of either gene suppressed proliferation, clonogenicity, migration, and tumor growth, while attenuating neuroendocrine features in vitro and in vivo. Spatial mapping, functional perturbation, and stromal-epithelial co-culture experiments mechanistically established a therapy-induced DPT+ fibroblast-complement circuit that enforced immune evasion and channels epithelial trajectories toward CRPC or neuroendocrine prostate cancer. Collectively, these findings defined the DPT+-complement-macrophage axis as an actionable vulnerability and position TSPAN1 and NRXN1 as therapeutic entry points to disrupt ADT-driven tumor ecosystem remodeling in prostate cancer.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer’s disease, and cancer. However, its potential neuroprotective effects on Parkinson’s disease (PD) have not yet been explored. The present study aimed to investigate the protective effects and underlying mechanisms of DMDD in a cellular model of PD. In this study, SH-SY5Y cells were incubated with or without DMDD following intoxication with the parkinsonian neurotoxin 1-methyl-4-phenylpyridine (MPP+). Cell viability and apoptosis were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) assay and Hoechst 33,342 staining, respectively. The mitochondrial membrane potential (Δψm) was assessed through the JC-10 assay. The activities of superoxide dismutase (SOD) and the levels of reactive oxygen species (ROS) were measured using WST-8 and DCFH-DA assays. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore significant biological processes and pathways influenced by DMDD. Molecular docking was employed to predict the domains of potential protein targets interacting with DMDD. Western blotting was subsequently conducted to determine the protein expression levels of TH, Nrf2, Bax, Bcl-2, Caspase-3, Beclin-1, PARP, LC3-II, LC3-I, p-PI3K, PI3K, p-mTOR and mTOR. Our study showed that DMDD treatment significantly increased cell viability and reduced apoptosis in MPP+-treated SH-SY5Y cells. In addition, DMDD treatment reversed the loss of TH expression and Δψm in MPP+-exposed SH-SY5Y cells. Moreover, DMDD treatment reduced MPP+-induced ROS production by promoting SOD activity. Additionally, compared with those in the MPP+ group, the protein expression levels of Beclin-1, Caspase-3, and PARP and the LC3II/I ratio were significantly decreased, whereas the protein expression levels of Nrf2 and the Bcl-2/Bax, p-PI3K/PI3K, and p-mTOR/mTOR ratios were significantly increased in the DMDD-treated group. In conclusion, DMDD protects against MPP+-induced cytotoxicity by mitigating oxidative stress, apoptosis, and autophagy. PI3K/mTOR signaling at least partly mediates the cytoprotective effect of DMDD.

BackgroundPituitary tumor-transforming gene 1 (PTTG1) is an important gene in tumour development. However, the relevance of PTTG1 in tumour prognosis, immunotherapy response, and medication sensitivity in human pan-cancer has to be determined.MethodsTIMER, GEPIA, the human protein atlas, GEPIA, TISCH2, and cBioportal examined the gene expression, protein expression, prognostic value, and genetic modification landscape of PTTG1 in 33 malignancies based on the TCGA cohort. The association between PTTG1 and tumour immunity, tumour microenvironment, immunotherapy response, and anticancer drug sensitivity was investigated using GSCA, TIDE, and CellMiner CDB. Molecular docking was used to validate the possible chemotherapeutic medicines for PTTG1. Additionally, siRNA-mediated knockdown was employed to confirm the probable role of PTTG1 in paclitaxel-resistant cells.ResultsPTTG1 is overexpressed and associated with poor survival in most tumors. Functional enrichment study revealed that PTTG1 is involved in the cell cycle and DNA replication. A substantial connection between PTTG1 expression and immune cell infiltration points to PTTG1's possible role in the tumour microenvironment. High PTTG1 expression is associated with tumour immunotherapy resistance. The process could be connected to PTTG1, which mediates T cell exhaustion and promotes cytotoxic T lymphocyte malfunction. Furthermore, PTTG1 was found to be substantially linked with sensitivity to several anticancer medications. Suppressing PTTG1 with siRNA reduced clone formation and migration, implying that PTTG1 may play a role in paclitaxel resistance.ConclusionPTTG1 shows potential as a cancer diagnostic, prognostic, and chemosensitivity marker. Increased PTTG1 expression is linked to resistance to cancer treatment. The mechanism could be linked to PTTG1's role in promoting cytotoxic T lymphocyte dysfunction and mediating T cell exhaustion. It is feasible to consider PTTG1, which is expressed on Treg and Tprolif cells, as a new therapeutic target for overcoming immunotherapy resistance.

Cognitive dysfunction has been accepted as a possible complication of type 2 diabetes (T2D), but few studies revealed the potential roles of Long non‑coding RNAs (lncRNAs) in cognitive dysfunction in T2D. The current research aims to demonstrate the specific expression patterns of lncRNA-mRNA in the hippocampi of T2D db/db mice exhibiting cognitive impairment. In this study, the results from behavioral tests showed that T2D db/db mice displayed short-term and spatial working memory deficits compared to db/m mice. Furthermore, western blot analysis demonstrated that compared with db/m mice, p-GSK3β (ser9) protein levels were markedly elevated in T2D db/db mice (P < 0.01). In addition, though not statistically significant, the ratio of p-Tau (Ser396) to Tau 46, α-Synuclein expression, and p-GSK3α (ser21) expression were also relatively higher in T2D db/db mice than in db/m mice. The microarray profiling revealed that 75 lncRNAs and 26 mRNAs were dysregulated in T2D db/db mice (> 2.0 fold change, P < 0.05). GO analysis demonstrated that the differentially expressed mRNAs participated in immune response, extracellular membrane-bounded organelle, and extracellular region. KEGG analysis revealed that the differentially expressed mRNAs were mainly involved in one carbon pool by folate, glyoxylate and dicarboxylate metabolism, autophagy, glycine, serine and threonine metabolism, and B cell receptor signaling pathway. A lncRNA‑mRNA coexpression network containing 71 lncRNAs and 26 mRNAs was built to investigate the interaction between lncRNA and mRNA. Collectively, these results revealed the differential hippocampal expression profiles of lncRNAs in T2D mice with cognitive dysfunction, and the findings from this study provide new clues for exploring the potential roles of lncRNAs in the pathogenesis of cognitive dysfunction in T2D.

目的 探讨α-突触核蛋白预制原纤维(α-Syn PFF)纹状体注射后能否生成病理性α-突触核蛋白(α-Syn),并从纹状体传播至嗅球,从而引起嗅球中神经元损伤.方法 3只健康雌性食蟹猴双侧纹状体注射α-Syn PFF作为实验组,以脑立体定向注射手术,将300 μg α-Syn PFF(7 g/L)注射到双侧纹状体的6个位点,即每侧纹状体壳核头部注射60 μg,体部注射60 μg,尾部注射30 μg.另2只健康雌性食蟹猴相同部位注射同等剂量磷酸盐缓冲液(PBS)作为对照组.注射2年后,实验猴行安乐死,取出嗅球经固定和切片,然后经尼氏染色检测组织病理改变,免疫组织化学染色检测磷酸化α-Syn(pS129)、酪氨酸羟化酶(TH)、双皮质素(DCX)的表达情况.结果 实验组与对照组比较,嗅球中存在pS129阳性聚集体;实验组TH和DCX阳性神经元数量较对照组均显著减少[TH:(27.00±11.22)个vs.(65.80±36.54)个;DCX:(67.60±17.23)个vs.(88.30±19.89)个].结论 食蟹猴纹状体注射α-Syn PFF产生的病理性α-Syn可从纹状体传播至嗅球造成嗅球神经元损伤,诱导嗅球中多巴胺能神经元丢失,并抑制新生神经元生成.

BACKGROUND:Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems.METHODS:We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network.RESULTS:In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes.CONCLUSIONS:Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa.

目的:基于单细胞RNA测序探究人正常肾脏中SOX9阳性祖细胞的转录组特征,为肾脏再生医学研究提供依据.方法:从GEO数据库中收集已发表的人类正常肾脏的单细胞RNA测序数据,结合差异基因分析、功能富集分析和拟时序分析探究SOX9阳性祖细胞的转录组特征,通过免疫组化实验和免疫荧光实验验证相关分析结果.结果:在人正常肾脏组织中,SOX9阳性细胞主要存在于近端小管中;GO分析结果显示,近端小管中的SOX9阳性细胞仍维持祖细胞样特性;进一步的亚群分析显示,近端小管SOX9阳性细胞可分为C1、C2和C33个亚群,其中C2亚群高表达SOX4、HES1、MYC、KLF4等与干细胞状态维持的相关基因,并在SOX9阳性细胞分化轨迹中处于起始位置.结论:人正常肾脏SOX9阳性细胞中仍有一部分细胞维持祖细胞样特性,具有潜在的再生医学研究价值.

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

目的 探讨长期高血糖对链脲佐菌素诱导的1型糖尿病(T1 DM)食蟹猴左心室心肌组织超微结构的影响.方法 通过静脉注射链脲佐菌素诱导构建T1 DM食蟹猴模型为模型组,正常食蟹猴为对照组,运用透射电镜观察模型组和对照组的左心室心肌组织超微结构并进行定量分析.结果 与对照组相比,模型组左心室心肌细胞胞质中线粒体数量减少(P<0.01),单位线粒体面积内相对电子密度、线粒体体积密度、表面积密度均降低(P<0.0001,P<0.001,P<0.05),差异有统计学意义;而线粒体表面积体积比、线粒体平均面积差异无统计学意义;左心室心肌细胞胞质中脂滴增多,左心室心肌微血管内皮细胞吞饮小泡数量减少、基底膜增厚(P<0.0001).结论 长期高血糖引起T1 DM食蟹猴左心室心肌细胞和心肌微血管内皮细胞结构受损.

帕金森病(PD)是一种以黑质多巴胺能神经元丢失为主要病理特征的神经退行性疾病,其病因不清且发病机制复杂.目前药物和手术治疗还难以根治PD.细胞治疗为PD治疗提供了新的策略,通过移植胎儿腹侧中脑组织至患者纹状体,可使患者运动功能得到一定程度的恢复,证实细胞移植具有治疗PD的作用;干细胞,包括多能干细胞、神经干细胞和间充质干细胞通过定向分化为多巴胺能神经元,为临床应用提供了可再生的细胞来源,进一步拓展了细胞治疗的前景;诱导神经元治疗PD避免了建立体外干细胞库的高成本,有望实现神经元原位再生.就基于不同细胞来源的PD细胞移植治疗研究进展进行综述,以期为再生医学治疗PD提供新的方向.

Multiple studies have been performed to map the kidney landscape of human and rodent, along with the development of sequencing technique. Although rodent disease models have been widely applied, many disadvantages also exist. Non-human primates (NHPs) are considered as the closest experimental animals to humans and show great advantages in the construction of animal models of human disease. Therefore, a comprehensive understanding of the heterogeneity and homogeneity between human and multiple animal kidney cells is important for further establishing animal models of human renal disease. Here, we generated the first single-cell transcriptome data of normal adult cynomolgus monkey kidney using 10x Genomics scRNA-seq platform. Then, we further performed an in-depth comparison across species at the single-cell level, and our analysis indicated that the gene expression of adult primate kidney cells showed a better correlation with human kidney than mouse kidney. Furthermore, our results demonstrated that the cellular localization of GWAS-identified renal disease genes showed differences across species. The cellular localization of blood pressure associated genes in human displayed similarity to cynomolgus monkey. This study provided a reliable reference for further studies associated with renal diseases on NHPs. In addition, our results also provided a novel insight into the choice of renal disease animal model and a detailed explanation for close genetic relationship between NHPs and human at a single cell level.

帕金森病(PD)是第二常见的神经退行性疾病.已有研究表明α-突触核蛋白(α-syn)与PD的发病有着密切的关系.国内外研究者利用α-syn的异位表达、过表达或脑内注射等方法来建立PD动物模型.近年来,α-突触核蛋白预制原纤维(α-syn PFFs)已用于动物模型的构建.α-syn PFFs在研究PD的起源及神经元病变传播中起促进作用.这些模型与传统化学毒素模型相比能够更好地复制PD患者特征性病理改变.本文基于α-syn的PD动物模型的研究进展进行综述.

Diabetes mellitus (DM) is an independent risk factor for cognitive impairment. Although the etiology of diabetic cognitive impairment is complex and multifactorial, the hippocampus neuronal apoptosis is recognized as a main cause of diabetes-induced cognitive impairment. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD was safe and effective in delaying some diabetic complications. However, the efficacy of DMDD to ameliorate diabetic cognitive impairment in type 2 diabetes mice has not been reported. In the present study, the behavioral evaluation was performed by Y maze and novel object recognition in db/db mice. Gene expression profiles were detected using mouse lncRNA microarray analysis in the hippocampi of db/db mice. Changes in the neurodegeneration-associated proteins and the apoptosis-related proteins were determined in both db/db mice and high glucose-treated HT22 cells by Western blotting. We observed that DMDD treatment significantly ameliorated the spatial working memory and object recognition memory impairment in db/db mice. Further study showed that neurodegeneration-associated protein tau was decreased after DMDD treatment in the hippocampi of db/db mice. Eleven lncRNAs and four mRNAs including pro-apoptotic gene Hif3a were significantly differently expressed after DMDD treatment in the hippocampi of db/db mice. The expression of Hif3a, cleaved parp, and caspase 3 proteins was significantly increased in the hippocampi of diabetic db/db mice compared with db/m control mice and then decreased after DMDD treatment. Similar beneficial effects of DMDD were observed in HG-treated HT22 cells. These data indicate that DMDD can alleviate cognitive impairment by inhibiting neuronal apoptosis through decreasing the expression of pro-apoptotic protein Hif3a. In conclusion, our study suggests that DMDD has great potential to be a new preventive and therapeutic compound for diabetic cognitive impairment.

Background: 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1,4-Dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD is a small molecular compound with significant therapeutic potential for tumors. However, the potential targets and pharmacological mechanism of DMDD to treat lung cancer has not been reported. Methods: We employed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of DMDD against lung cancer. Potential therapeutic targets of DMDD were screened by PharmMapper. Differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA) lung cancer data sets were extracted and analyzed by GEPIA2. The mechanism of DMDD against lung cancer was determined by PPI, gene ontology (GO) and KEGG pathway enrichment analysis. Survival analysis and molecular docking were employed to obtain the key targets of DMDD. Human lung cancer cell lines H1975 and PC9 were used to detect effects of DMDD treatment in vitro. The expression of key targets after DMDD treated was validated by Western Blot. Results: A total of 60 Homo sapiens potential therapeutic targets of DMDD and 3,545 DEGs in TCGA lung cancer datasets were identified. Gene ontology and pathway analysis revealed characteristic of the potential targets of DMDD and DEGs in lung cancer respectively. Cell cycle and pathways in cancer were overlapping with DMDD potential targets and lung cancer DEGs. Eight overlapping genes were found between DMDD potential therapeutic targets and lung cancer related DEGs. Survival analysis showed that high expression of DMDD potential targets CCNE1 and E2F1 was significantly related to poor patient survival in lung cancer. Molecular docking found that DMDD exhibited significant binding affinities within the active site of CCNE1 and E2F1. Further tests showed that DMDD inhibited the proliferation, migration and clone formation in lung cancer cell lines (H1975 and PC9) in a dose and time dependent manner. Mechanistically, DMDD treatment decreased the expression of CDK2, CCNE1, E2F1 proteins and induced cell cycle arrest at the G1/S phase in H1975 and PC9 cells. Conclusion: These results delineated that DMDD holds therapeutic potential that blocks tumorigenesis by cell cycle regulation in lung cancer, and may provide potential therapies for lung cancer.

BACKGROUND:Prostate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented.METHODS:The cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa.RESULTS:Based on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels.CONCLUSIONS:Our study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.

目的 构建一种可高效支持人胚胎干细胞生长的人源饲养层细胞系.方法 首先通过在TW2R细胞系稳定表达人E-钙黏素(E-cadherin)基因构建永生化人源饲养层细胞系TWE3R,并比较人胚胎干细胞在TWE3R及其亲本细胞上的克隆形成数.将H9人胚胎干细胞在TWE3R细胞上经过10代连续传代培养后,进行人胚胎干细胞特异性标志物分析、拟胚体形成分析和畸胎瘤形成检测等实验.结果 本研究成功构建了永生化的人源饲养层细胞系TWE3R,TWE3R细胞可比其亲本细胞更高效地支持人胚胎干细胞生长,并且TWE3R饲养层细胞还具有支持低密度接种条件下(每平方厘米5个)人胚胎干细胞生长的特性.此外,H9人胚胎干细胞在TWE3R细胞上长期传代培养后,仍可保持所有人胚胎干细胞的未分化特性、正常细胞核型以及在体内外均可分化形成所有3个胚层衍生物的潜能.结论 本研究所建立的永生化人源饲养层细胞系TWE3R具有高效支持胚胎干细胞生长的特性.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies. Attempts have been directed to accommodate the increasing population of patients with T1DM. Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients. In this review, we discuss the current research advances in strategies to obtain insulin-producing cells (IPCs) from different precursor cells and in stem cell-based therapies for diabetes.

目的:基于已发表的芯片数据通过生物信息学方法筛选差异表达基因,以发现前列腺癌诊断/预后和耐药相关分子标志物.方法:筛选GEO数据库中已发表的前列腺癌mRNA芯片数据GSE6956和前列腺癌细胞多烯紫杉醇耐药mRNA芯片数据GSE33455进行差异表达分析;通过生物学功能注释、基因通路富集分析、蛋白质相互作用网络(protein-protein interaction,PPI)分析等生物信息学方法发现和识别与差异表达基因相关的生物学功能和信号通路;比对TCGA数据库,验证差异表达基因在前列腺癌组织及癌旁组织中的表达,并通过Kaplan-Meier分析差异表达基因对前列腺癌患者生存率的影响;用qPCR方法验证差异表达基因在前列腺癌细胞株PC3及多烯紫杉醇耐药细胞PC3-DTX中的表达情况.结果:共筛选出227个在前列腺癌和前列腺癌多烯紫杉醇耐药细胞芯片数据中共同差异表达基因.差异表达基因主要富集到了癌症相关通路(Lysosome、Sphingolipid、FoxO、Acute myeloid leukemia),并主要参与细胞黏附、自噬和胞内蛋白转运等生物学过程.构建PPI网络选取18个连接度最高的基因作为Hub基因.Hub基因和共同差异表达基因中,上调基因CITED2、LRP12和RPL17-C18orf32与前列腺癌患者的不良预后显著相关.qPCR验证显示CITED2在多烯紫杉醇耐药细胞PC3-DTX中高表达.结论:通过生物信息学方法筛选出在前列腺癌组织和耐药细胞中共同差异表达,且与前列腺癌患者的不良预后密切相关的基因,为前列腺癌诊断/预后和耐药分子标志物的研究提供了新的思路.

A comprehensive cellular anatomy of normal human kidney is crucial to address the cellular origins of renal disease and renal cancer. Some kidney diseases may be cell type-specific, especially renal tubular cells. To investigate the classification and transcriptomic information of the human kidney, we rapidly obtained a single-cell suspension of the kidney and conducted single-cell RNA sequencing (scRNA-seq). Here, we present the scRNA-seq data of 23,366 high-quality cells from the kidneys of three human donors. In this dataset, we show 10 clusters of normal human renal cells. Due to the high quality of single-cell transcriptomic information, proximal tubule (PT) cells were classified into three subtypes and collecting ducts cells into two subtypes. Collectively, our data provide a reliable reference for studies on renal cell biology and kidney disease.