Protein & CellPub Date : 2025-08-09DOI: 10.1093/procel/pwaf056
{"title":"Correction to: Endothelial-to-Osteoblast Conversion maintains bone homeostasis through Kindlin-2/Piezo1/TGFβ/Runx2 axis.","authors":"","doi":"10.1093/procel/pwaf056","DOIUrl":"https://doi.org/10.1093/procel/pwaf056","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"6 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825271","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}
{"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":"10.1093/procel/pwaf001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"685-704"},"PeriodicalIF":12.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342163/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cryo-EM structures of Nipah virus polymerase complex reveal highly varied interactions between L and P proteins among paramyxoviruses.","authors":"Lu Xue, Tiancai Chang, Jiacheng Gui, Zimu Li, Heyu Zhao, Binqian Zou, Junnan Lu, Mei Li, Xin Wen, Shenghua Gao, Peng Zhan, Lijun Rong, Liqiang Feng, Peng Gong, Jun He, Xinwen Chen, Xiaoli Xiong","doi":"10.1093/procel/pwaf014","DOIUrl":"10.1093/procel/pwaf014","url":null,"abstract":"<p><p>Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"705-723"},"PeriodicalIF":12.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450206","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}
{"title":"Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation.","authors":"Min Wang, Zan He, Anqi Wang, Shuhui Sun, Jiaming Li, Feifei Liu, Chunde Li, Chengxian Yang, Jinghui Lei, Yan Yu, Shuai Ma, Si Wang, Weiqi Zhang, Zhengrong Yu, Guang-Hui Liu, Jing Qu","doi":"10.1093/procel/pwaf025","DOIUrl":"10.1093/procel/pwaf025","url":null,"abstract":"<p><p>Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"667-684"},"PeriodicalIF":12.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677110","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}
{"title":"Systematic analyses uncover plasma proteins linked to incident cardiovascular diseases.","authors":"Yi-Lin Chen, Ji-Jing Wang, Jia You, Ji-Yun Cheng, Ze-Yu Li, Yi-Jun Ge, Bing-Ran Yao, Xiao-Yu He, Yu Guo, Yi Zhang, Shi-Dong Chen, Liu Yang, Xin-Rui Wu, Bang-Sheng Wu, Ya-Ru Zhang, Mei Cui, Qiang Dong, Jian-Feng Feng, Mei Tian, Wei Cheng, Jin-Tai Yu","doi":"10.1093/procel/pwaf072","DOIUrl":"https://doi.org/10.1093/procel/pwaf072","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) research is hindered by limited comprehensive analyses of plasma proteome across disease subtypes. Here, we systematically investigated the associations between plasma proteins and cardiovascular outcomes in 53,026 UK Biobank participants over a 14-year follow-up. Association analyses identified 3,089 significant associations involving 892 unique protein analytes across 13 CVD outcomes. The most notable associations included NT-proBNP for atrial fibrillation (P = 6.31 × 10-313), followed by NPPB (P = 1.03 × 10-164) and GDF15 for heart failure (P = 1.21 × 10-166). Among 445 unique proteins significantly linked to 18 cardiovascular metrics, LEP (RVEDV: β = -9.03, P = 2.76 × 10-51) and FABP4 (RVEDV: β = -10.18, P = 2.42 × 10-32) emerged as the strongest correlates of cardiac structure and function. Our integrated prediction model performed excellently across the majority of CVD outcomes, achieving an AUC of 0.86 for abdominal aneurysm. Two-sample Mendelian randomization analysis revealed 225 proteins causally linked to CVDs, with LPA showing the strongest coronary artery disease association (OR = 1.13 [1.10-1.17], P = 2.38 × 10-15), many of which are targets of existing drugs, suggesting repurposing opportunities. Mediation analysis revealed broad-spectrum mediators (e.g., IGFBP4 and GDF15, each influencing 9 cardiovascular outcomes) and outcome-specific protein mediators, with modifiable risk factors such as smoking and BMI predominantly mediating protein-CVD associations.This comprehensive longitudinal study provides unprecedented insights into plasma proteome influences on cardiovascular health interactions, offering novel perspectives for CVD diagnosis, prediction, and prevention.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030404","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}
Protein & CellPub Date : 2025-08-04DOI: 10.1093/procel/pwaf070
Duo Su,Mengyun Deng,Lingfei Hu,Hao Xie,Bo Yang,Huiying Yang,Dongsheng Zhou
{"title":"A cell differentiation landscape for monocyte and interstitial macrophage in the lung with diffuse alveolar damage.","authors":"Duo Su,Mengyun Deng,Lingfei Hu,Hao Xie,Bo Yang,Huiying Yang,Dongsheng Zhou","doi":"10.1093/procel/pwaf070","DOIUrl":"https://doi.org/10.1093/procel/pwaf070","url":null,"abstract":"Diffuse alveolar damage (DAD) is recognized as a deadly type of acute inflammatory lung injury caused by toxic inhalants, but its cellular and molecular pathogenesis remains largely unclear. In this study, by using a mouse model of ricin-induced DAD, we explored the heterogeneity of recruited monocyte (Mono) and Mono-derived interstitial macrophage (IM) in the DAD lung. There was the development of 2 distinct IM subsets, namely IMpi (pro-inflammatory) and IMai (anti-inflammatory), from recruited Monopi. A subset of recruited Monopi could get the proliferating phenotype (namely pMonopi), and meanwhile pMonopi served as the intermediate of Monopi-to-IMai transition. The presence of growth differentiation factor 15 (GDF15) facilitated Monopi-to-pMonopi-to-IMai transition, whereas GDF15 deficiency exerted the negative feedback effect of enhancing Monopi-to-IMpi shift. These findings provided a cell differentiation landscape for Mono and IM in the DAD lung, which would promote a deeper understanding of cellular immunology of DAD and offer a theoretical basis for developing novel therapeutic strategies against acute lung injury.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"15 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825268","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}