Protein & Cell最新文献_第9页

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner. 人 ESC 衍生血管细胞以 HIF-1α 依赖性方式促进血管再生。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-01-03 DOI: 10.1093/procel/pwad027

Jinghui Lei, Xiaoyu Jiang, Daoyuan Huang, Ying Jing, Shanshan Yang, Lingling Geng, Yupeng Yan, Fangshuo Zheng, Fang Cheng, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Si Wang, Jing Qu

{"title":"Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner.","authors":"Jinghui Lei, Xiaoyu Jiang, Daoyuan Huang, Ying Jing, Shanshan Yang, Lingling Geng, Yupeng Yan, Fangshuo Zheng, Fang Cheng, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Si Wang, Jing Qu","doi":"10.1093/procel/pwad027","DOIUrl":"10.1093/procel/pwad027","url":null,"abstract":"Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"36-51"},"PeriodicalIF":21.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9432828","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

Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction. 对妇科肿瘤和生殖中染色体外环状 DNA 的创新见解。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-01-03 DOI: 10.1093/procel/pwad032

Ning Wu, Ling Wei, Zhipeng Zhu, Qiang Liu, Kailong Li, Fengbiao Mao, Jie Qiao, Xiaolu Zhao

{"title":"Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.","authors":"Ning Wu, Ling Wei, Zhipeng Zhu, Qiang Liu, Kailong Li, Fengbiao Mao, Jie Qiao, Xiaolu Zhao","doi":"10.1093/procel/pwad032","DOIUrl":"10.1093/procel/pwad032","url":null,"abstract":"Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"6-20"},"PeriodicalIF":21.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524639","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

Correction to: SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. 更正：SIRT7作为异染色质稳定剂拮抗人类干细胞衰老

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-01-03 DOI: 10.1093/procel/pwad037

引用次数: 0

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement. RBM42 的双叶变体会导致神经、面部、心脏和肌肉骨骼受累的多系统疾病。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-01-03 DOI: 10.1093/procel/pwad034

Yiyao Chen, Bingxin Yang, Xiaoyu Merlin Zhang, Songchang Chen, Minhui Wang, Liya Hu, Nina Pan, Shuyuan Li, Weihui Shi, Zhenhua Yang, Li Wang, Yajing Tan, Jian Wang, Yanlin Wang, Qinghe Xing, Zhonghua Ma, Jinsong Li, He-Feng Huang, Jinglan Zhang, Chenming Xu

{"title":"Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.","authors":"Yiyao Chen, Bingxin Yang, Xiaoyu Merlin Zhang, Songchang Chen, Minhui Wang, Liya Hu, Nina Pan, Shuyuan Li, Weihui Shi, Zhenhua Yang, Li Wang, Yajing Tan, Jian Wang, Yanlin Wang, Qinghe Xing, Zhonghua Ma, Jinsong Li, He-Feng Huang, Jinglan Zhang, Chenming Xu","doi":"10.1093/procel/pwad034","DOIUrl":"10.1093/procel/pwad034","url":null,"abstract":"Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"52-68"},"PeriodicalIF":21.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603681","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

An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral. 一种可口服的单价 SMAC 拟态化合物，是一种广谱抗病毒药物。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-01-03 DOI: 10.1093/procel/pwad033

Miao Mei, Maria Antonietta Impagnatiello, Jun Jiao, Ulrich Reiser, Ulrike Tontsch-Grunt, Ju Zhang, Paul Nicklin, Bingke Yu, Yu Wang, Yuan He, Xu Tan

引用次数: 0

Strategies for generating mouse model resources of human disease. 产生人类疾病小鼠模型资源的策略。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2023-12-01 DOI: 10.1093/procel/pwad011

Jirong Pan, Ling Zhang, Zhibing Huang, Dalu Zhao, He Li, Yanan Fu, Meng Wang, Borui Chen, Fuad A Iraqi, Grant Morahan, Chuan Qin

引用次数: 1

Deciphering the placental abnormalities associated with somatic cell nuclear transfer at single-nucleus resolution. 在单核分辨率下解读与体细胞核移植相关的胎盘异常。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2023-12-01 DOI: 10.1093/procel/pwad030

Liyuan Jiang, Xin Wang, Leyun Wang, Sinan Ma, Yali Ding, Chao Liu, Siqi Wang, Xuan Shao, Ying Zhang, Zhikun Li, Wei Li, Guihai Feng, Qi Zhou

引用次数: 1

CRISPR-assisted transcription activation by phase-separation proteins. 通过相分离蛋白的crispr辅助转录激活。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2023-12-01 DOI: 10.1093/procel/pwad013

Jiaqi Liu, Yuxi Chen, Baoting Nong, Xiao Luo, Kaixin Cui, Zhan Li, Pengfei Zhang, Wenqiong Tan, Yue Yang, Wenbin Ma, Puping Liang, Zhou Songyang

{"title":"CRISPR-assisted transcription activation by phase-separation proteins.","authors":"Jiaqi Liu, Yuxi Chen, Baoting Nong, Xiao Luo, Kaixin Cui, Zhan Li, Pengfei Zhang, Wenqiong Tan, Yue Yang, Wenbin Ma, Puping Liang, Zhou Songyang","doi":"10.1093/procel/pwad013","DOIUrl":"10.1093/procel/pwad013","url":null,"abstract":"The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"874-887"},"PeriodicalIF":21.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9140892","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: 2

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis. 灵长类动物睾丸衰老的单核转录组图谱揭示了精原干细胞储存库的衰竭和支持细胞稳态的丧失。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2023-12-01 DOI: 10.1093/procel/pwac057

Daoyuan Huang, Yuesheng Zuo, Chen Zhang, Guoqiang Sun, Ying Jing, Jinghui Lei, Shuai Ma, Shuhui Sun, Huifen Lu, Yusheng Cai, Weiqi Zhang, Fei Gao, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang

{"title":"A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.","authors":"Daoyuan Huang, Yuesheng Zuo, Chen Zhang, Guoqiang Sun, Ying Jing, Jinghui Lei, Shuai Ma, Shuhui Sun, Huifen Lu, Yusheng Cai, Weiqi Zhang, Fei Gao, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang","doi":"10.1093/procel/pwac057","DOIUrl":"10.1093/procel/pwac057","url":null,"abstract":"The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"888-907"},"PeriodicalIF":21.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476820","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: 6

Cryo-EM structures of a prokaryotic heme transporter CydDC. 原核血红素转运蛋白CydDC的低温电镜结构。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2023-12-01 DOI: 10.1093/procel/pwad022

Chen Zhu, Yanfeng Shi, Jing Yu, Wenhao Zhao, Lingqiao Li, Jingxi Liang, Xiaolin Yang, Bing Zhang, Yao Zhao, Yan Gao, Xiaobo Chen, Xiuna Yang, Lu Zhang, Luke W Guddat, Lei Liu, Haitao Yang, Zihe Rao, Jun Li

引用次数: 0