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Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T cell differentiation. 染色质景观改变揭示了记忆 CD8+ T 细胞分化过程中的多个转录回路。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-13 DOI: 10.1093/procel/pwaf003
Qiao Liu, Wei Dong, Rong Liu, Luming Xu, Ling Ran, Ziying Xie, Shun Lei, Xingxing Su, Zhengliang Yue, Dan Xiong, Lisha Wang, Shuqiong Wen, Yan Zhang, Jianjun Hu, Chenxi Qin, Yongchang Chen, Bo Zhu, Xiangyu Chen, Xia Wu, Lifan Xu, Qizhao Huang, Yingjiao Cao, Lilin Ye, Zhonghui Tang
{"title":"Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T cell differentiation.","authors":"Qiao Liu, Wei Dong, Rong Liu, Luming Xu, Ling Ran, Ziying Xie, Shun Lei, Xingxing Su, Zhengliang Yue, Dan Xiong, Lisha Wang, Shuqiong Wen, Yan Zhang, Jianjun Hu, Chenxi Qin, Yongchang Chen, Bo Zhu, Xiangyu Chen, Xia Wu, Lifan Xu, Qizhao Huang, Yingjiao Cao, Lilin Ye, Zhonghui Tang","doi":"10.1093/procel/pwaf003","DOIUrl":"https://doi.org/10.1093/procel/pwaf003","url":null,"abstract":"<p><p>Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971978","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
Oncomicrobial vaccines mitigate tumor progression via precisely targeting oncomicrobes in mice.
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-07 DOI: 10.1093/procel/pwae067
Yudan Mao, Yan Li, Xianzun Xiao, Junrui Mai, Gan Lin, Sheng Liu, Jiayuan Huang, Xiangting Zhou, Xiangyu Mou, Wenjing Zhao
{"title":"Oncomicrobial vaccines mitigate tumor progression via precisely targeting oncomicrobes in mice.","authors":"Yudan Mao, Yan Li, Xianzun Xiao, Junrui Mai, Gan Lin, Sheng Liu, Jiayuan Huang, Xiangting Zhou, Xiangyu Mou, Wenjing Zhao","doi":"10.1093/procel/pwae067","DOIUrl":"https://doi.org/10.1093/procel/pwae067","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953972","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
Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study. 慢病毒修饰造血干细胞基因疗法治疗晚期症状性幼年变色性白质营养不良症:长期跟踪试点研究。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-04 DOI: 10.1093/procel/pwae037
Zhao Zhang, Hua Jiang, Li Huang, Sixi Liu, Xiaoya Zhou, Yun Cai, Ming Li, Fei Gao, Xiaoting Liang, Kam-Sze Tsang, Guangfu Chen, Chui-Yan Ma, Yuet-Hung Chai, Hongsheng Liu, Chen Yang, Mo Yang, Xiaoling Zhang, Shuo Han, Xin Du, Ling Chen, Wuh-Liang Hwu, Jiacai Zhuo, Qizhou Lian
{"title":"Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.","authors":"Zhao Zhang, Hua Jiang, Li Huang, Sixi Liu, Xiaoya Zhou, Yun Cai, Ming Li, Fei Gao, Xiaoting Liang, Kam-Sze Tsang, Guangfu Chen, Chui-Yan Ma, Yuet-Hung Chai, Hongsheng Liu, Chen Yang, Mo Yang, Xiaoling Zhang, Shuo Han, Xin Du, Ling Chen, Wuh-Liang Hwu, Jiacai Zhuo, Qizhou Lian","doi":"10.1093/procel/pwae037","DOIUrl":"10.1093/procel/pwae037","url":null,"abstract":"<p><p>Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"16-27"},"PeriodicalIF":13.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446854","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
Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate aging in mice. 非编码 RNA Terc-53 和透明质酸受体 Hmmr 可调节小鼠的衰老。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-04 DOI: 10.1093/procel/pwae023
Sipeng Wu, Yiqi Cai, Lixiao Zhang, Xiang Li, Xu Liu, Guangkeng Zhou, Hongdi Luo, Renjian Li, Yujia Huo, Zhirong Zhang, Siyi Chen, Jinliang Huang, Jiahao Shi, Shanwei Ding, Zhe Sun, Zizhuo Zhou, Pengcheng Wang, Geng Wang
{"title":"Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate aging in mice.","authors":"Sipeng Wu, Yiqi Cai, Lixiao Zhang, Xiang Li, Xu Liu, Guangkeng Zhou, Hongdi Luo, Renjian Li, Yujia Huo, Zhirong Zhang, Siyi Chen, Jinliang Huang, Jiahao Shi, Shanwei Ding, Zhe Sun, Zizhuo Zhou, Pengcheng Wang, Geng Wang","doi":"10.1093/procel/pwae023","DOIUrl":"10.1093/procel/pwae023","url":null,"abstract":"<p><p>One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"28-48"},"PeriodicalIF":13.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892318","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
ARID1A IDR targets EWS-FLI1 condensates and finetunes chromatin remodeling. ARID1A IDR以EWS-FLI1凝集物为靶标,对染色质重塑进行微调。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-04 DOI: 10.1093/procel/pwae029
Jingdong Xue, Siang Lv, Ming Yu, Yixuan Pan, Ningzhe Li, Xiang Xu, Qi Zhang, Mengyuan Peng, Fang Liu, Xuxu Sun, Yimin Lao, Yanhua Yao, Juan Song, Jun Wu, Bing Li
{"title":"ARID1A IDR targets EWS-FLI1 condensates and finetunes chromatin remodeling.","authors":"Jingdong Xue, Siang Lv, Ming Yu, Yixuan Pan, Ningzhe Li, Xiang Xu, Qi Zhang, Mengyuan Peng, Fang Liu, Xuxu Sun, Yimin Lao, Yanhua Yao, Juan Song, Jun Wu, Bing Li","doi":"10.1093/procel/pwae029","DOIUrl":"10.1093/procel/pwae029","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"64-71"},"PeriodicalIF":13.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959284","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
Molecular architecture of mammalian pyruvate dehydrogenase complex. 哺乳动物丙酮酸脱氢酶复合物的分子结构。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-04 DOI: 10.1093/procel/pwae044
Maofei Chen, Yutong Song, Sensen Zhang, Yitang Zhang, Xudong Chen, Minghui Zhang, Meng Han, Xin Gao, Sai Li, Maojun Yang
{"title":"Molecular architecture of mammalian pyruvate dehydrogenase complex.","authors":"Maofei Chen, Yutong Song, Sensen Zhang, Yitang Zhang, Xudong Chen, Minghui Zhang, Meng Han, Xin Gao, Sai Li, Maojun Yang","doi":"10.1093/procel/pwae044","DOIUrl":"10.1093/procel/pwae044","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"72-78"},"PeriodicalIF":13.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047111","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
PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression. PDHX 乙酰化通过破坏 PDC 组装和激活乳化介导的基因表达,促进肿瘤进展。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-04 DOI: 10.1093/procel/pwae052
Zetan Jiang, Nanchi Xiong, Ronghui Yan, Shi-Ting Li, Haiying Liu, Qiankun Mao, Yuchen Sun, Shengqi Shen, Ling Ye, Ping Gao, Pinggen Zhang, Weidong Jia, Huafeng Zhang
{"title":"PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression.","authors":"Zetan Jiang, Nanchi Xiong, Ronghui Yan, Shi-Ting Li, Haiying Liu, Qiankun Mao, Yuchen Sun, Shengqi Shen, Ling Ye, Ping Gao, Pinggen Zhang, Weidong Jia, Huafeng Zhang","doi":"10.1093/procel/pwae052","DOIUrl":"10.1093/procel/pwae052","url":null,"abstract":"<p><p>Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"49-63"},"PeriodicalIF":13.6,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293998","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
Structural insights into the distinct ligand recognition and signaling of the chemerin receptors CMKLR1 and GPR1.
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-01-03 DOI: 10.1093/procel/pwae073
Xiaowen Lin, Lechen Zhao, Heng Cai, Xiaohua Chang, Yuxuan Tang, Tianyu Luo, Mengdan Wu, Cuiying Yi, Limin Ma, Xiaojing Chu, Shuo Han, Qiang Zhao, Beili Wu, Maozhou He, Ya Zhu
{"title":"Structural insights into the distinct ligand recognition and signaling of the chemerin receptors CMKLR1 and GPR1.","authors":"Xiaowen Lin, Lechen Zhao, Heng Cai, Xiaohua Chang, Yuxuan Tang, Tianyu Luo, Mengdan Wu, Cuiying Yi, Limin Ma, Xiaojing Chu, Shuo Han, Qiang Zhao, Beili Wu, Maozhou He, Ya Zhu","doi":"10.1093/procel/pwae073","DOIUrl":"https://doi.org/10.1093/procel/pwae073","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927961","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 minimally invasive, fast on/off "Odorgenetic" method to manipulate physiology.
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-12-31 DOI: 10.1093/procel/pwae072
Yanqiong Wu, Xueqin Xu, Shanchun Su, Zeyong Yang, Xincai Hao, Wei Lu, Jianghong He, Juntao Hu, Xiaohui Li, Hong Yu, Xiuqin Yu, Yangqiao Xiao, Shuangshuang Lu, Linhan Wang, Wei Tian, Hongbin Xiang, Gang Cao, Wen Jun Tu, Changbin Ke
{"title":"A minimally invasive, fast on/off \"Odorgenetic\" method to manipulate physiology.","authors":"Yanqiong Wu, Xueqin Xu, Shanchun Su, Zeyong Yang, Xincai Hao, Wei Lu, Jianghong He, Juntao Hu, Xiaohui Li, Hong Yu, Xiuqin Yu, Yangqiao Xiao, Shuangshuang Lu, Linhan Wang, Wei Tian, Hongbin Xiang, Gang Cao, Wen Jun Tu, Changbin Ke","doi":"10.1093/procel/pwae072","DOIUrl":"https://doi.org/10.1093/procel/pwae072","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910403","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
Preparation of fatty acid solutions for investigating lipid signaling, metabolism, and lipid droplets. 制备脂肪酸溶液,用于研究脂质信号、新陈代谢和脂滴。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-12-17 DOI: 10.1093/procel/pwae068
Shuyan Zhang, Mengwei Zhang, Shimeng Xu, Xiaochuan Fu, Qiumin Liao, Bin Pan, Liujuan Cui, Pingsheng Liu
{"title":"Preparation of fatty acid solutions for investigating lipid signaling, metabolism, and lipid droplets.","authors":"Shuyan Zhang, Mengwei Zhang, Shimeng Xu, Xiaochuan Fu, Qiumin Liao, Bin Pan, Liujuan Cui, Pingsheng Liu","doi":"10.1093/procel/pwae068","DOIUrl":"https://doi.org/10.1093/procel/pwae068","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839023","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
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