Cell ResearchPub Date : 2026-07-21DOI: 10.1038/s41422-026-01281-1
Mert Gayretli, Jacob H. Hanna
{"title":"Signaling-independent boosting of human blastoid formation","authors":"Mert Gayretli, Jacob H. Hanna","doi":"10.1038/s41422-026-01281-1","DOIUrl":"10.1038/s41422-026-01281-1","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 9","pages":"637-638"},"PeriodicalIF":31.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-026-01281-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552291","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}
Cell ResearchPub Date : 2026-07-13DOI: 10.1038/s41422-026-01277-x
Kathy O. Lui, Bin Zhou
{"title":"A new era of lineage tracing","authors":"Kathy O. Lui, Bin Zhou","doi":"10.1038/s41422-026-01277-x","DOIUrl":"10.1038/s41422-026-01277-x","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 8","pages":"565-566"},"PeriodicalIF":31.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432726","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}
Cell ResearchPub Date : 2026-07-13DOI: 10.1038/s41422-026-01275-z
Zhifei Shi, Xiyang Chen, Yijia Yang, Ang Wu, Heng Wang, Kai Chen, Chong Li, Lina Zou, Zhipeng Qu, Yuyan Zhao, Wenjing Gan, Shuhui Li, Jiayu Chen, Wenqiang Liu, Jiejun Shi, Hong Wang, Jia-min Zhang, Chenfei Wang, Shaorong Gao, Xiaoyu Liu
{"title":"Genome-wide profiling of histone modifications and transcription factor binding at single-cell resolution by DeChIC-seq","authors":"Zhifei Shi, Xiyang Chen, Yijia Yang, Ang Wu, Heng Wang, Kai Chen, Chong Li, Lina Zou, Zhipeng Qu, Yuyan Zhao, Wenjing Gan, Shuhui Li, Jiayu Chen, Wenqiang Liu, Jiejun Shi, Hong Wang, Jia-min Zhang, Chenfei Wang, Shaorong Gao, Xiaoyu Liu","doi":"10.1038/s41422-026-01275-z","DOIUrl":"10.1038/s41422-026-01275-z","url":null,"abstract":"Mapping of protein-DNA interactions at single-cell resolution remains a central challenge in epigenomics, particularly for transcription factors (TFs), whose sparse binding limits reliable detection. Here, we establish DeChIC-seq (DNA Deaminase-based Chromatin Immuno-Conversion sequencing), a conversion-based strategy that uses a protein A-DddAtox fusion to directly record protein-DNA interactions by inducing localized C-to-U conversions near antibody-bound chromatin. Retaining genome-wide background sequence information without immunoprecipitation, DeChIC-seq enables profiling of histone modifications and sensitive detection of TF binding. Integration with single-cell whole-genome amplification extends DeChIC-seq to single-cell applications (scDeChIC-seq), enabling chromatin profiling of individual cells. Applied to mouse embryogenesis, scDeChIC-seq resolves lineage-specific chromatin states through profiling of H3K4me3, CTCF, and RAD21 and sensitively detects TF binding, including that of NR5A2, TFAP2C, and KLF5, from extremely limited blastomere inputs. This underscores its strong potential for detecting TF-binding sites in scarce biological samples. DeChIC-seq establishes a conversion-based framework for chromatin profiling that enables mechanistic dissection of TF-driven gene regulation across rare cells, developmental systems, and disease contexts.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 9","pages":"680-697"},"PeriodicalIF":31.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432725","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}
Cell ResearchPub Date : 2026-07-13DOI: 10.1038/s41422-026-01276-y
Duo Wang, Hao Ming, Dongshan Yang, Xiang Cui, Zachary Freeman, Li-Kuang Tsai, Zhuying Wei, Liu Liu, Giovanna Nascimento Scatolin, Brian Bennett, Xiukun Wang, Kimberly Yau, Litao Tao, Xinyi Tong, Shuling Wang, Kai-Xuan Shi, Denis Evseenko, Ben Van Handel, Longhua Guo, Xiaoting Dai, Youcai Xiong, Bingjing Zhang, Yinjuan Wang, Rajan Iyyappan, Oscar Alejandro Ojeda-Rojas, Guang Hu, Lynda McGinnis, Richard Paulson, Daniel Mckim, Xiangbo Kong, Xiaofeng Xia, Jifeng Zhang, Y. Eugene Chen, Zongliang Jiang, Jie Xu, Qi-Long Ying
{"title":"A universal 6iL/E4 culture system for deriving and maintaining embryonic stem cells across mammalian species","authors":"Duo Wang, Hao Ming, Dongshan Yang, Xiang Cui, Zachary Freeman, Li-Kuang Tsai, Zhuying Wei, Liu Liu, Giovanna Nascimento Scatolin, Brian Bennett, Xiukun Wang, Kimberly Yau, Litao Tao, Xinyi Tong, Shuling Wang, Kai-Xuan Shi, Denis Evseenko, Ben Van Handel, Longhua Guo, Xiaoting Dai, Youcai Xiong, Bingjing Zhang, Yinjuan Wang, Rajan Iyyappan, Oscar Alejandro Ojeda-Rojas, Guang Hu, Lynda McGinnis, Richard Paulson, Daniel Mckim, Xiangbo Kong, Xiaofeng Xia, Jifeng Zhang, Y. Eugene Chen, Zongliang Jiang, Jie Xu, Qi-Long Ying","doi":"10.1038/s41422-026-01276-y","DOIUrl":"10.1038/s41422-026-01276-y","url":null,"abstract":"The derivation of authentic embryonic stem cells (ESCs) across mammalian species remains a major challenge. Here, we report the development of a defined, serum-free culture system, termed 6iL/E4, that enables the derivation and long-term self-renewal of ESCs across diverse mammalian species. Through systematic dissection of signaling pathways, we identified conserved regulatory modules involving GSK3α, WNT, STAT3, PDGFR, and MEK/ERK signaling. The optimized 6iL/E4 conditions support stable derivation and expansion of ESCs from mouse, rat, rabbit, and bovine embryos. For rabbit, ESC derivation required supplementation with the LATS inhibitor TDI-011536 (TDI), and 6iL/TDI-cultured rabbit ESCs exhibited chimera-forming capability. In bovine ESCs, inducible expression of Klf2 and Nanog reinforced pluripotency and promoted in vivo chimeric contribution. Importantly, we demonstrated that 6iL robustly establishes and maintains human pluripotent stem cells in a naïve-like state. These findings reveal conserved principles underlying ESC self-renewal across divergent mammalian species and provide a universal platform for cross-species stem cell research, disease modeling, and biotechnological applications.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 8","pages":"611-628"},"PeriodicalIF":31.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-026-01276-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435313","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}
Cell ResearchPub Date : 2026-07-03DOI: 10.1038/s41422-026-01273-1
Jiao Qin, Chenxi Cai, Mayu Shan, Suqing Zhou, Qingya Shen, Tianyi Zhu, Mingming Zhao, Yang Mei, Fanghan Ji, Dan-Dan Shen, Shao-Kun Zang, Huibing Zhang, Haomang Xu, Ming Yang, Wei-Wei Wang, Rong Xiao, Bing Yang, Chunyou Mao, Zhenhua Shao, Haijing Wu, Qianjin Lu, Yan Zhang
{"title":"Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2","authors":"Jiao Qin, Chenxi Cai, Mayu Shan, Suqing Zhou, Qingya Shen, Tianyi Zhu, Mingming Zhao, Yang Mei, Fanghan Ji, Dan-Dan Shen, Shao-Kun Zang, Huibing Zhang, Haomang Xu, Ming Yang, Wei-Wei Wang, Rong Xiao, Bing Yang, Chunyou Mao, Zhenhua Shao, Haijing Wu, Qianjin Lu, Yan Zhang","doi":"10.1038/s41422-026-01273-1","DOIUrl":"10.1038/s41422-026-01273-1","url":null,"abstract":"C5a, the most potent anaphylatoxin in the complement system, exerts its effects through the canonical G protein-coupled receptor C5aR1 and the arrestin-coupled receptor C5aR2. Despite the critical role of C5aR2 in immunomodulation, the molecular mechanisms underlying its biased signaling, ligand recognition, and associated pathophysiology remain poorly understood. Here, we report cryo-electron microscopy structures of β-arrestin 1-bound C5aR2 and C5aR1 stimulated by C5a or its metabolite C5adesArg. By combining structural analysis with functional assays, we identified the key structural determinants that prevent G protein coupling and confer intrinsic bias toward β-arrestins. Comparative analysis elucidated the distinct ligand recognition mechanism of C5aR2 and explained the retained affinity of C5adesArg for C5aR2. These findings guided the rational design of ZQ105, a highly selective C5aR2 agonist. Leveraging ZQ105 as a chemical probe, functional studies revealed that selective C5aR2 activation induces distinct pro-inflammatory responses and receptor internalization in neutrophils. This study provides novel structural insights into transducer engagement and ligand recognition by C5aR2, yielding a valuable pharmacological tool for exploring C5aR2-related pathophysiological processes.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 9","pages":"718-733"},"PeriodicalIF":31.1,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379685","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}
Cell ResearchPub Date : 2026-07-01DOI: 10.1038/s41422-026-01271-3
Haipeng Fu, Alan R. Saltiel
{"title":"One drug, five targets","authors":"Haipeng Fu, Alan R. Saltiel","doi":"10.1038/s41422-026-01271-3","DOIUrl":"10.1038/s41422-026-01271-3","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 10","pages":"739-740"},"PeriodicalIF":31.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-026-01271-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367127","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}