Protein & CellPub Date : 2025-02-13DOI: 10.1093/procel/pwaf010
Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li
{"title":"Setd2 overexpression rescues bivalent gene expression during SCNT-mediated ZGA.","authors":"Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li","doi":"10.1093/procel/pwaf010","DOIUrl":"https://doi.org/10.1093/procel/pwaf010","url":null,"abstract":"<p><p>Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3 and H3K27me3. Additionally, it reinstated the expression levels of ZGA-related genes by re-establishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410165","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 : 2025-02-12DOI: 10.1093/procel/pwaf005
{"title":"Correction to: Advances in gene and cellular therapeutic approaches for Huntington's disease.","authors":"","doi":"10.1093/procel/pwaf005","DOIUrl":"https://doi.org/10.1093/procel/pwaf005","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410164","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 : 2025-02-01DOI: 10.1093/procel/pwae048
Heng Zhang, Zhiwei Zheng, Xiaoying Chen, Lizhen Xu, Chen Guo, Jiawei Wang, Yihui Cui, Fan Yang
{"title":"RADICAL: a rationally designed ion channel activated by ligand for chemogenetics.","authors":"Heng Zhang, Zhiwei Zheng, Xiaoying Chen, Lizhen Xu, Chen Guo, Jiawei Wang, Yihui Cui, Fan Yang","doi":"10.1093/procel/pwae048","DOIUrl":"10.1093/procel/pwae048","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"136-142"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120399","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}
Protein & CellPub Date : 2025-02-01DOI: 10.1093/procel/pwae026
Qiuyang Zheng, Xin Wang
{"title":"Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy.","authors":"Qiuyang Zheng, Xin Wang","doi":"10.1093/procel/pwae026","DOIUrl":"10.1093/procel/pwae026","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the leading cause of dementia, is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. This condition casts a significant shadow on global health due to its complex and multifactorial nature. In addition to genetic predispositions, the development of AD is influenced by a myriad of risk factors, including aging, systemic inflammation, chronic health conditions, lifestyle, and environmental exposures. Recent advancements in understanding the complex pathophysiology of AD are paving the way for enhanced diagnostic techniques, improved risk assessment, and potentially effective prevention strategies. These discoveries are crucial in the quest to unravel the complexities of AD, offering a beacon of hope for improved management and treatment options for the millions affected by this debilitating disease.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"83-120"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909164","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}
Protein & CellPub Date : 2025-01-15DOI: 10.1093/procel/pwaf002
Han Liu,Hongye Zeng,Xiaojing Qin,Wenjing Ning,Lin Xu,Shiting Yang,Xue Liu,Wenxin Luo,Ningshao Xia
{"title":"The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts.","authors":"Han Liu,Hongye Zeng,Xiaojing Qin,Wenjing Ning,Lin Xu,Shiting Yang,Xue Liu,Wenxin Luo,Ningshao Xia","doi":"10.1093/procel/pwaf002","DOIUrl":"https://doi.org/10.1093/procel/pwaf002","url":null,"abstract":"Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence (AI), in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"127 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989315","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 : 2025-01-13DOI: 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}