Protein & Cell最新文献

Gene print-based cell subtypes annotation of human disease across heterogeneous datasets with gPRINT.

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-14 DOI: 10.1093/procel/pwaf001

Ruojin Yan, Chunmei Fan, Shen Gu, Tingzhang Wang, Zi Yin, Xiao Chen

{"title":"Gene print-based cell subtypes annotation of human disease across heterogeneous datasets with gPRINT.","authors":"Ruojin Yan, Chunmei Fan, Shen Gu, Tingzhang Wang, Zi Yin, Xiao Chen","doi":"10.1093/procel/pwaf001","DOIUrl":"https://doi.org/10.1093/procel/pwaf001","url":null,"abstract":"Identification of disease-specific cell subtypes (DSCSs) has profound implications for understanding disease mechanisms, preoperative diagnosis, and precision therapy. However, achieving unified annotation of DSCSs in heterogeneous single-cell datasets remains a challenge. In this study, we developed the gPRINT algorithm (generalized approach for cell subtype Identification with single cell's voicePRINT). Inspired by the principles of speech recognition in noisy environments, gPRINT transforms gene position and gene expression information into voiceprints based on ordered and clustered gene expression phenomena, obtaining unique \"gene print\" patterns for each cell. Then, we integrated neural networks to mitigate the impact of background noise on cell identity label mapping. We demonstrated the reproducibility of gPRINT across different donors, single-cell sequencing platforms, and disease subtypes, and its utility for automatic cell subtype annotation across datasets. Moreover, gPRINT achieved higher annotation accuracy of 98.37% when externally validated based on the same tissue, surpassing other algorithms. Furthermore, this approach has been applied to fibrosis-associated diseases in multiple tissues throughout the body, as well as to the annotation of fibroblast subtypes in a single tissue, tendon, where fibrosis is prevalent. We successfully achieved automatic prediction of tendinopathy-specific cell subtypes, key targets, and related drugs. In summary, gPRINT provides an automated and unified approach for identifying DSCSs across datasets, facilitating the elucidation of specific cell subtypes under different disease states and providing a powerful tool for exploring therapeutic targets in diseases.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel loop-structure-based bispecific CAR that targets CD19 and CD22 with enhanced therapeutic efficacy against B-cell malignancies. 基于环路结构的新型双特异性 CAR，靶向 CD19 和 CD22，提高了对 B 细胞恶性肿瘤的疗效。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-08 DOI: 10.1093/procel/pwae034

Lijun Zhao, Shuhong Li, Xiaoyi Wei, Xuexiu Qi, Qiaoru Guo, Licai Shi, Ji-Shuai Zhang, Jun Li, Ze-Lin Liu, Zhi Guo, Hongyu Zhang, Jia Feng, Yuanyuan Shi, Suping Zhang, Yu J Cao

引用次数: 0

High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome. 高通量单微生物 RNA 测序揭示了人类肠道微生物组的适应状态异质性和宿主-噬菌体活动关联。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-08 DOI: 10.1093/procel/pwae027

Yifei Shen, Qinghong Qian, Liguo Ding, Wenxin Qu, Tianyu Zhang, Mengdi Song, Yingjuan Huang, Mengting Wang, Ziye Xu, Jiaye Chen, Ling Dong, Hongyu Chen, Enhui Shen, Shufa Zheng, Yu Chen, Jiong Liu, Longjiang Fan, Yongcheng Wang

{"title":"High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome.","authors":"Yifei Shen, Qinghong Qian, Liguo Ding, Wenxin Qu, Tianyu Zhang, Mengdi Song, Yingjuan Huang, Mengting Wang, Ziye Xu, Jiaye Chen, Ling Dong, Hongyu Chen, Enhui Shen, Shufa Zheng, Yu Chen, Jiong Liu, Longjiang Fan, Yongcheng Wang","doi":"10.1093/procel/pwae027","DOIUrl":"10.1093/procel/pwae027","url":null,"abstract":"Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"211-226"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens. 磷脂酰肌醇-4,5-二磷酸的内分解代谢是建立抵御病原体能力的基础。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-08 DOI: 10.1093/procel/pwae041

Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi

{"title":"Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.","authors":"Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi","doi":"10.1093/procel/pwae041","DOIUrl":"10.1093/procel/pwae041","url":null,"abstract":"Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"161-187"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses. IL-24 通过驱动 MRSA 诱导的过敏反应，促进特应性皮炎样炎症。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-08 DOI: 10.1093/procel/pwae030

Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng

{"title":"IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.","authors":"Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng","doi":"10.1093/procel/pwae030","DOIUrl":"10.1093/procel/pwae030","url":null,"abstract":"Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"188-210"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BiFC and FACS-based CRISPR screening revealed that QKI promotes PABPN1 LLPS in colorectal cancer cells.

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-07 DOI: 10.1093/procel/pwaf022

Mengxia Li, Zhijie Hu, Yingye Huang, Yuting Han, Cheng Liang, Yuchi Liu, Runze Wu, Xin Lu, Ke Deng, Susu Liu, Xin Ou, Yuwei Li, Chao Liu, Xuening Li, Jingting Liang, Yonggui Fu, Anlong Xu

引用次数: 0

Pasteurized Akkermansia muciniphila promotes GP2 expression in microfold cells and facilitates Salmonella infection. 巴氏杀菌的 Akkermansia muciniphila 可促进微折细胞中 GP2 的表达，并促进沙门氏菌感染。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-03-03 DOI: 10.1093/procel/pwaf017

Wenhui Zhang, Gan Xi, Huaiwu Zhang, Jinmiao Bi, Tongtong Zhou, Junhao Zhu, Zhan Zhang, Shuo Wang, Moshi Song, Jun Wang

引用次数: 0

Mechanistic insights into the GEF activity of the human MON1A/CCZ1/C18orf8 complex. 人类 MON1A/CCZ1/C18orf8 复合物 GEF 活性的机制研究。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-02-28 DOI: 10.1093/procel/pwaf018

Yubin Tang, Yaoyao Han, Zhenpeng Guo, Ying Li, Xinyu Gong, Yuchao Zhang, Haobo Liu, Xindi Zhou, Daichao Xu, Yixiao Zhang, Lifeng Pan

引用次数: 0

Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis.

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-02-25 DOI: 10.1093/procel/pwaf020

Hongshuai Jia, Guang Yue, Pin Li, Renjun Peng, Ruyue Jin, Yuhan Chen, Hualin Cao, Kangning Yang, Xiaowei Zhang, Xiaoyu Yi, Yangyang Wu, Xiangling Deng, Xiaoye Chen, Lifei Ma, Yang Zhao, Xiaoguang Zhou, Tian Tao, Xiaoli Shen, Xu Zhang, Yuandong Tao, Huixia Zhou

{"title":"Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis.","authors":"Hongshuai Jia, Guang Yue, Pin Li, Renjun Peng, Ruyue Jin, Yuhan Chen, Hualin Cao, Kangning Yang, Xiaowei Zhang, Xiaoyu Yi, Yangyang Wu, Xiangling Deng, Xiaoye Chen, Lifei Ma, Yang Zhao, Xiaoguang Zhou, Tian Tao, Xiaoli Shen, Xu Zhang, Yuandong Tao, Huixia Zhou","doi":"10.1093/procel/pwaf020","DOIUrl":"https://doi.org/10.1093/procel/pwaf020","url":null,"abstract":"Renal fibrosis is a common mechanism leading to kidney failure in chronic kidney diseases (CKDs), including obstructive nephropathy (ON). Dysregulated inflammation is central to the development of renal fibrosis, but how local immune cells within the tissue microenvironment integrate and coordinate to drive this condition remains largely unknown. Herein, we documented that neutrophils were abundantly recruited and expelled neutrophil extracellular traps (NETs) in human and mouse fibrotic kidneys. Importantly, circulating levels of NET components displayed a significant correlation with worsened kidney function in ON patients. In the unilateral ureteral obstruction (UUO) mouse model, blocking NETs by protein-arginine deiminase type 4 (PAD4) deletion or DNase treatment significantly impaired NET formation and inhibited renal fibrosis and inflammation, whereas NET adoptive transfer exacerbated the fibrotic process. Moreover, NET-mediated renal fibrosis was associated with enhanced infiltration of cytotoxic CD8+ T cells, which produced granzyme B (GZMB) to drive tubular cell epithelial-mesenchymal transition (EMT) and fibroblast activation. Accordingly, pharmacological inhibition of GZMB resulted in blunted kidney inflammation and fibrosis. Furthermore, NETs profoundly potentiated the production of T-cell chemokines CXCL9/10/11 in macrophages, but not in tubular cells or fibroblasts, thus driving T-cell infiltration and fueling inflammatory cascades in the kidneys. Mechanistically, the NET-macrophage interaction was partially mediated by the TLR2/4 signaling. Thus, our work reveals a previously unexplored role of the collaboration between NETs and macrophages in supporting CD8+ T cell infiltration, which orchestrates kidney inflammation and fibrosis.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amino acid metabolism in breast cancer: Pathogenic drivers and therapeutic opportunities.

IF 13.6 1区生物学

Protein & Cell Pub Date : 2025-02-20 DOI: 10.1093/procel/pwaf011

Yawen Liu, Xiangyun Zong, Patricia Altea-Manzano, Jie Fu

{"title":"Amino acid metabolism in breast cancer: Pathogenic drivers and therapeutic opportunities.","authors":"Yawen Liu, Xiangyun Zong, Patricia Altea-Manzano, Jie Fu","doi":"10.1093/procel/pwaf011","DOIUrl":"https://doi.org/10.1093/procel/pwaf011","url":null,"abstract":"Amino acid metabolism plays a critical role in the progression and development of breast cancer. Cancer cells, including those in breast cancer, reprogram amino acid metabolism to meet the demands of rapid proliferation, survival, and immune evasion. This includes alterations in the uptake and utilization of amino acids such as glutamine, serine, glycine, and arginine, which provide essential building blocks for biosynthesis, energy production, and redox homeostasis. Notably, the metabolic phenotypes of breast cancer cells vary across molecular subtypes and disease stages, emphasizing the need for patient stratification and personalized therapeutic strategies. Advances in multi-level diagnostics, including phenotyping and predictive tools such as AI-based analysis and body fluid profiling, have highlighted the potential for tailoring treatments to individual metabolic profiles. Enzymes such as glutaminase and serine hydroxymethyltransferase, often upregulated in breast cancer, represent promising therapeutic targets. Understanding the interplay between amino acid metabolism and breast cancer biology, alongside the integration of personalized medicine approaches, can uncover novel insights into tumor progression and guide the development of precision therapies. This review explores the metabolic pathways of amino acids in breast cancer, with a focus on their implications for personalized treatment strategies.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0