Cell Research最新文献_第3页

Modeling post-gastrula development via bidirectional pluripotent stem cells. 通过双向多能干细胞模拟原肠胚后发育。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-29 DOI: 10.1038/s41422-025-01172-x

Kuisheng Liu, Zihui Yan, Dandan Bai, Rui Jiang, Yan Bi, Xiangjun Ma, Jiani Xiang, Yifan Sheng, Baoxing Dong, Zhiyuan Ning, Shanru Yi, Yingdong Liu, Xinyi Lei, Yanping Jia, Yan Zhang, Yalin Zhang, Yanhe Li, Tao Wu, Chenxiang Xi, Shanyao Liu, Shuyi Liu, Jiayu Chen, Jiqing Yin, Xiaochen Kou, Yanhong Zhao, Hong Wang, Yixuan Wang, Ke Wei, Shaorong Gao, Wenqiang Liu

{"title":"Modeling post-gastrula development via bidirectional pluripotent stem cells.","authors":"Kuisheng Liu, Zihui Yan, Dandan Bai, Rui Jiang, Yan Bi, Xiangjun Ma, Jiani Xiang, Yifan Sheng, Baoxing Dong, Zhiyuan Ning, Shanru Yi, Yingdong Liu, Xinyi Lei, Yanping Jia, Yan Zhang, Yalin Zhang, Yanhe Li, Tao Wu, Chenxiang Xi, Shanyao Liu, Shuyi Liu, Jiayu Chen, Jiqing Yin, Xiaochen Kou, Yanhong Zhao, Hong Wang, Yixuan Wang, Ke Wei, Shaorong Gao, Wenqiang Liu","doi":"10.1038/s41422-025-01172-x","DOIUrl":"https://doi.org/10.1038/s41422-025-01172-x","url":null,"abstract":"<p><p>The absence of stem cells capable of efficiently generating both trophoblast and epiblast lineages has hindered precise recapitulation of embryonic development. Through high-content chemical screening, we established an (AS and LY) AL medium to generate mouse bidirectional pluripotent stem cells (BPSCs) characterized by concurrent expression of OCT4 and CDX2. Mouse BPSCs demonstrated highly plastic differentiation into trophoblast, epiblast and primitive endoderm (PrE) lineages in vitro within 48 h without exogenous inducing factors and efficiently contributed to embryonic and extraembryonic tissues in vivo. Mechanistically, hyperactivation of the Wnt signaling pathway breaks the early lineage differentiation barrier by initiating a Lef1-dependent bypass. Remarkably, integration of BPSCs with PrE induction system enables high-efficiency generation of E8.5-stage embryo models. These advanced models complete gastrulation and recapitulate definitive developmental milestones including brain morphogenesis, neural tube closure, cardiac contraction, somite patterning, and primordial germ cell specification. Moreover, human cells cultured under AL conditions acquire an OCT4 and CDX2 double-positive state and corresponding gene expression profiles, revealing conserved functionality of this culturing platform across species. These findings highlight BPSCs as a powerful tool for investigating early lineage specification and post-gastrulation embryonic development.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":25.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944816","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

Novel organoid culture condition: modeling fetal-like plasticity in colorectal cancer 新型类器官培养条件：模拟结直肠癌胎儿样可塑性。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-29 DOI: 10.1038/s41422-025-01170-z

Chao Wu, Min Jung Kim, J. Joshua Smith

引用次数: 0

Sabotaging TCR signaling-LAG3 interferes with the CD3ε-LCK interaction. 破坏TCR信号- lag3干扰CD3ε-LCK相互作用。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-22 DOI: 10.1038/s41422-025-01168-7

Gina J Fiala, Wolfgang W Schamel

引用次数: 0

A decade of migrasome research: biogenesis, physiological functions, and disease implications 十年来偏头痛研究：生物发生、生理功能和疾病影响。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-22 DOI: 10.1038/s41422-025-01153-0

Jinqiang Yu, Li Yu

引用次数: 0

Broad-spectrum plant immunity: engineering pathogen protease-activated autoactive NLRs. 广谱植物免疫：工程病原体蛋白酶激活的自体NLRs。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-20 DOI: 10.1038/s41422-025-01169-6

Qibin Wu, Wanying Zhao, Zheng Qing Fu, Youxiong Que

引用次数: 0

SIX of one and half-a-dozen USP2 regulating inflammation 6个半打USP2调节炎症。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-20 DOI: 10.1038/s41422-025-01173-w

Lin Liu, John Silke

引用次数: 0

AlphaCD: a machine learning model capable of highly accurate characterization for 21,335 cytidine deaminases alphaacd：一种机器学习模型，能够高度准确地表征21,335种胞苷脱氨酶。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-18 DOI: 10.1038/s41422-025-01164-x

Kui Xu, Guoying Hua, Mingdi Wu, Haihang Zhang, Jingda Liu, Hu Feng, Erwei Zuo

{"title":"AlphaCD: a machine learning model capable of highly accurate characterization for 21,335 cytidine deaminases","authors":"Kui Xu, Guoying Hua, Mingdi Wu, Haihang Zhang, Jingda Liu, Hu Feng, Erwei Zuo","doi":"10.1038/s41422-025-01164-x","DOIUrl":"10.1038/s41422-025-01164-x","url":null,"abstract":"The vast scope but limited-supporting evidence in sequence databases hinders identification of proteins with specific functionality. Here, we experimentally characterized catalytic efficiency, target site window, motif preference, and off-target activity of 1100 apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-like family cytidine deaminases (CDs) fused with nCas9 in HEK293T cells, thereby generating the largest dataset of experimentally validated functions for a single protein family to date. These data, together with amino acid sequence, three-dimensional structure, and eight additional features, were used to construct a machine learning (ML) model, AlphaCD, which showed high accuracy in predicting catalytic efficiency (0.92) and off-target activity (0.84), as well as target windows (0.73) and catalytic motifs (0.78). We applied the trained model to predict the above catalytic features of 21,335 CDs in Uniprot, and subsampling of 28 CDs further validated its prediction accuracy (0.84, 0.87, 0.75, 0.73, respectively). Alanine scanning-based mutagenesis was then employed to reduce off-targets in one example CD, which produced a remarkably high fidelity, high efficiency cytosine base editor, thus demonstrating AlphaCD application in high-accuracy, high-throughput protein functional characterization, and providing a strategy for accelerated characterization of other proteins.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 10","pages":"750-761"},"PeriodicalIF":25.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871708","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

Lung cell fates during influenza 流感期间肺细胞的死亡。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-18 DOI: 10.1038/s41422-025-01163-y

Brianna Jarboe, Maria Shubina, Ryan A. Langlois, David F. Boyd, Siddharth Balachandran

{"title":"Lung cell fates during influenza","authors":"Brianna Jarboe, Maria Shubina, Ryan A. Langlois, David F. Boyd, Siddharth Balachandran","doi":"10.1038/s41422-025-01163-y","DOIUrl":"10.1038/s41422-025-01163-y","url":null,"abstract":"Roughly 1 billion people are infected by Influenza A viruses (IAVs) worldwide each year, resulting in approximately half a million deaths. Particularly concerning is the threat of IAV spillover from avian and other animal reservoirs. The recent outbreak of highly pathogenic avian influenza H5N1 in US dairy cows highlights this concern. While viruses that enter human populations from such zoonotic transmission typically lack the ability to transmit effectively between humans, they may be only a few mutations from acquiring this capacity. These newly adapted viruses have the potential to be significantly more virulent than seasonal strains. A major contributor to influenza pathology is the over-exuberant immune response to the virus, particularly when the infection is present in distal pulmonary tissues. Maladaptive immune pathway over-activation can drive tissue damage and pathology, often independently of effective viral control. Anti-inflammatories targeting host-initiated pathological processes hold promise, but these avenues require a thorough understanding of virus-triggered lung inflammation before they can be fully exploited. In this review, we will discuss recent advances in our understanding of the cell types that are targeted by IAV, the consequences of IAV infection on the biology of these cells, and their contribution to lung pathology in influenza. We will also discuss how virus-induced hyper-inflammatory responses present new entry-points for therapeutic intervention, showcasing Z-form nucleic acid-binding protein 1 (ZBP1)-initiated necroptosis as an example of one such pathway.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 10","pages":"707-718"},"PeriodicalIF":25.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01163-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871709","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

Constitutive arrestin recruitment by orphan GPR52 via an atypical binding mode 孤儿GPR52通过非典型结合模式招募本构性阻滞

IF 44.1 1区生物学

Cell Research Pub Date : 2025-08-15 DOI: 10.1038/s41422-025-01165-w

Xi Lin, Xiaohu Wei, Ning Pu, Ling Wang, Zhibin Zhang, Cuixia Li, Yang Yue, Junlin Liu, Qiwen Tan, Qianqian Sun, Fei Xu

引用次数: 0

Establishment of human gastrulating stem cells with the capacity of stable differentiation into multiple gastrulating cell types 建立具有稳定分化为多种原肠胚细胞类型的人原肠胚干细胞

IF 25.9 1区生物学

Cell Research Pub Date : 2025-08-06 DOI: 10.1038/s41422-025-01146-z

Mingqian Huang, Mengqi Chen, Gege Yuan, Yiqiang Cui, Bin Shen, Zhaode Liu, Bohang Zhang, Junqing Chen, Dingdong Chen, Shuangshuang Qiu, Yichun Zhang, Li Liu, Lianju Qin, Yunfei Zhu, Jiayin Liu, Hao Zhang, Jun Wu, Yan Yuan, Jiahao Sha

{"title":"Establishment of human gastrulating stem cells with the capacity of stable differentiation into multiple gastrulating cell types","authors":"Mingqian Huang, Mengqi Chen, Gege Yuan, Yiqiang Cui, Bin Shen, Zhaode Liu, Bohang Zhang, Junqing Chen, Dingdong Chen, Shuangshuang Qiu, Yichun Zhang, Li Liu, Lianju Qin, Yunfei Zhu, Jiayin Liu, Hao Zhang, Jun Wu, Yan Yuan, Jiahao Sha","doi":"10.1038/s41422-025-01146-z","DOIUrl":"10.1038/s41422-025-01146-z","url":null,"abstract":"Pluripotent stem cells (PSCs) have been derived from various species, but most culture systems stabilize only a single PSC type. By contrast, epiblast cells in vivo exist along a continuum and interact dynamically with both embryonic and extraembryonic cells, interactions missing in standard PSC cultures. This absence limits the self-organizing potential of PSCs and leads to disorganized tissue formation in teratomas. To address this, we developed a unified culture system that supports the stable differentiation of epiblast-like cells into multiple key human gastrulating cell types, collectively called human gastrulating stem cells (hGaSCs). hGaSCs, composed of endoderm-like, mesoderm-like, ectoderm-like, amnion ectoderm-like, and primordial germ cell-like cells, maintain a stable balance during long-term culture. In 3D culture, hGaSCs self-assemble into gastruloid-like structures (hGaSC-gastruloids) that model aspects of a Carnegie Stage 7 human embryo, including gastrulation and germ layer specification. Using hGaSC-gastruloids, we modeled the effects of valproic acid (VPA) on human gastrulation and uncovered molecular pathways underlying VPA-induced malformations. When transplanted into the seminiferous tubules, hGaSCs formed embryo-like structures, progressing through fetal tissue and organ development, unlike the disorganized growth seen in teratomas. In conclusion, hGaSCs provide a versatile platform to study human gastrulation, early organogenesis, developmental defects, and drug teratogenicity, with promising applications in tissue and organ generation from cultured stem cells.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 10","pages":"719-734"},"PeriodicalIF":25.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786740","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