Developmental cell最新文献_第5页

Decoding plant cell types across species: A blueprint for gene discovery 解码跨物种植物细胞类型：基因发现的蓝图

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-27 DOI: 10.1016/j.devcel.2025.08.007

Xin Tian, Jian Xu

引用次数: 0

A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro 小鼠体外模拟大脑皮层发育和顺式调控进化的类器官平台

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-27 DOI: 10.1016/j.devcel.2025.08.001

Daniel Medina-Cano, Mohammed T. Islam, Veronika Petrova, Sanjana Dixit, Zerina Balic, Marty G. Yang, Matthias Stadtfeld, Emily S. Wong, Thomas Vierbuchen

{"title":"A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro","authors":"Daniel Medina-Cano, Mohammed T. Islam, Veronika Petrova, Sanjana Dixit, Zerina Balic, Marty G. Yang, Matthias Stadtfeld, Emily S. Wong, Thomas Vierbuchen","doi":"10.1016/j.devcel.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.001","url":null,"abstract":"Natural selection has shaped the gene regulatory networks that orchestrate cortical development, leading to structural and functional variation across mammals, but the molecular and cellular mechanisms underpinning these changes have only begun to be characterized. Here, we develop a reproducible protocol for cerebral cortex organoid generation from mouse epiblast stem cells (EpiSCs), which recapitulates the timing and cellular differentiation programs of the embryonic cortex. We generated cortical organoids from F1 hybrid EpiSCs derived from crosses between laboratory mice (C57BL/6J) and four wild-derived inbred strains spanning ∼1 M years of evolutionary divergence to comprehensively map cis-acting transcriptional regulatory variation across developing cortical cell types, using single-cell RNA sequencing (scRNA-seq). We identify hundreds of genes that exhibit dynamic allelic imbalances, providing the first insight into the developmental mechanisms underpinning changes in cortical structure and function between subspecies. These experimental methods and cellular resources represent a powerful platform for investigating gene regulation in the developing cerebral cortex.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"28 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906070","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

Long-range deployment of tumor-antigen-specific cytotoxic T lymphocytes inhibits lung metastasis of breast cancer 肿瘤抗原特异性细胞毒性T淋巴细胞的远程部署抑制乳腺癌的肺转移

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-27 DOI: 10.1016/j.devcel.2025.08.003

Yue Xing, Yan Zhou, Ruxin Wang, Jianing Chen, Linbin Yang, Xiangyu Meng, Jiawen Wang, Qian Ouyang, Jinghua Zhao, Fei Chen, Phei Er Saw, Jia Fan, Jian-Dong Huang, Wei Wu, Qiang Liu, Erwei Song, Di Huang

{"title":"Long-range deployment of tumor-antigen-specific cytotoxic T lymphocytes inhibits lung metastasis of breast cancer","authors":"Yue Xing, Yan Zhou, Ruxin Wang, Jianing Chen, Linbin Yang, Xiangyu Meng, Jiawen Wang, Qian Ouyang, Jinghua Zhao, Fei Chen, Phei Er Saw, Jia Fan, Jian-Dong Huang, Wei Wu, Qiang Liu, Erwei Song, Di Huang","doi":"10.1016/j.devcel.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.003","url":null,"abstract":"Tumor-antigen-specific CD8+ T cells (CTLs) are the main effector immunocytes in anti-tumor immunity, but their systemic deployment against cancer metastasis remains uncharacterized. Here, we found that the abundance of tumor-specific CD103+CD8+ T cells in the tumor-draining lymph nodes (TDLNs) was associated with improved lung-metastasis-free survival in breast cancer patients. In mouse cancer models, CD103+CD8+ T cells were primed in TDLNs and recruited to the lungs via C-C motif chemokine ligand 5/receptor 9 (CCL25/CCR9) signaling to inhibit metastasis through antigen-specific immunity. Furthermore, extracellular vesicles (EVs) from early- and late-stage tumors differentially polarized alveolar macrophages to release CCL25 and IDO1, respectively, and the latter impaired pulmonary CD103+CD8+ T cell deployment, facilitating lung metastasis. Depleting IDO1 effectively rescued CD103+CD8+ T cell-mediated protection against lung metastasis. These findings exemplified long-range deployment of adaptive immunity to protect distant organs from metastasis, highlighting the therapeutic potential of reconstituting effector immune cell deployment (EICD) for cancer treatment.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"102 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906069","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

Loss of NOTCH2 creates a TRIM28-dependent vulnerability in small cell lung cancer NOTCH2缺失在小细胞肺癌中产生trim28依赖性易感性

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-26 DOI: 10.1016/j.devcel.2025.07.023

Deli Hong, Ying Lyu, Richa Nayak, Justin S. Becker, Matthew A. Booker, Keita Masuzawa, Zoe Devos, Tianchu Wang, Shin Saito, Qi Liu, Yixiang Li, Zhaorong Li, Eric H. Knelson, Tran Thai, Leslie Duplaquet, Yasmin N. Laimon, Gabriel Roberti De Oliveira, Sabina Signoretti, John G. Doench, David A. Barbie, Matthew G. Oser

{"title":"Loss of NOTCH2 creates a TRIM28-dependent vulnerability in small cell lung cancer","authors":"Deli Hong, Ying Lyu, Richa Nayak, Justin S. Becker, Matthew A. Booker, Keita Masuzawa, Zoe Devos, Tianchu Wang, Shin Saito, Qi Liu, Yixiang Li, Zhaorong Li, Eric H. Knelson, Tran Thai, Leslie Duplaquet, Yasmin N. Laimon, Gabriel Roberti De Oliveira, Sabina Signoretti, John G. Doench, David A. Barbie, Matthew G. Oser","doi":"10.1016/j.devcel.2025.07.023","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.023","url":null,"abstract":"Small cell lung cancer (SCLC) is a highly aggressive malignancy that lacks effective targeted therapies, in part due to frequent loss-of-function mutations in tumor suppressors and the absence of recurrent oncogenic drivers. Approximately 15% of SCLCs harbor inactivating mutations in NOTCH1 or NOTCH2, and most neuroendocrine-high SCLCs exhibit low NOTCH activity. Using CRISPR-Cas9 screening in primary cell lines derived from NOTCH1/2-isogenic SCLC genetically engineered mouse models, we identified TRIM28 as a synthetic lethal dependency in NOTCH2-inactivated SCLCs. Loss of TRIM28 in this context robustly induced expression of endogenous retroviruses (ERVs), activated viral sensing pathways, and triggered a type I interferon response. Mechanistically, NOTCH2 inactivation increased reliance on TRIM28-mediated ERV silencing, creating a hyperdependence on TRIM28 via the STING-MAVS-TBK1 axis. Notably, TRIM28 was essential for tumor growth only in the setting of NOTCH2 loss. These findings identify TRIM28 as a potential therapeutic target in NOTCH2-deficient or low-NOTCH2-expressing SCLC.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"13 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900395","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

Large-scale single-cell profiling of stem cells identifies redundant regulators of shoot development and yield trait variation 干细胞的大规模单细胞分析鉴定了茎发育和产量性状变异的冗余调节因子

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-26 DOI: 10.1016/j.devcel.2025.07.024

Xiaosa Xu, Michael Passalacqua, Brian Rice, Edgar Demesa-Arevalo, Mikiko Kojima, Yumiko Takebayashi, Xingyao Yu, Benjamin Harris, Yuchen Liu, Andrea Gallavotti, Hitoshi Sakakibara, Jesse Gillis, David Jackson

{"title":"Large-scale single-cell profiling of stem cells identifies redundant regulators of shoot development and yield trait variation","authors":"Xiaosa Xu, Michael Passalacqua, Brian Rice, Edgar Demesa-Arevalo, Mikiko Kojima, Yumiko Takebayashi, Xingyao Yu, Benjamin Harris, Yuchen Liu, Andrea Gallavotti, Hitoshi Sakakibara, Jesse Gillis, David Jackson","doi":"10.1016/j.devcel.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.024","url":null,"abstract":"Plant shoot stem cells generate organs essential for food, feed, and biofuels. However, plant single-cell analyses struggled to capture these rare cells or to detect stem cell regulators like CLAVATA3 and WUSCHEL. Here, we dissected stem cell-enriched shoot tissues from maize and Arabidopsis for single-cell RNA sequencing (scRNA-seq), and we optimized protocols to recover thousands of CLAVATA3- and WUSCHEL-expressing cells. A cross-species comparison identified deeply conserved stem cell regulators. We also profiled maize stem cell mutants, validated candidate regulators with spatial transcriptomics, and confirmed their roles in shoot development. These include a family of RNA-binding protein genes and two families of sugar kinase genes. Finally, we show how coupling large-scale single-cell profiling with allelic variation analysis in diverse maize germplasm serves as a valuable resource for identifying stem cell regulators significantly associated with grain yield components. Our discoveries advance the study of shoot stem cells and open avenues for rational crop engineering.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"16 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900394","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

Investigating morphogen and patterning dynamics with optogenetic control of morphogen production 利用光遗传控制研究形态发生和模式动力学

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-22 DOI: 10.1016/j.devcel.2025.07.019

Dirk Benzinger, James Briscoe

{"title":"Investigating morphogen and patterning dynamics with optogenetic control of morphogen production","authors":"Dirk Benzinger, James Briscoe","doi":"10.1016/j.devcel.2025.07.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.019","url":null,"abstract":"Morphogen gradients provide the patterning cues that instruct cell fate decisions during development. Here, we establish an optogenetic system for the precise spatiotemporal control <ce:italic>in vitro</ce:italic> of Sonic hedgehog (Shh) morphogen production. Using a tunable light-inducible gene expression system, we generate long-range Shh gradients that pattern mouse neural progenitors into spatially distinct domains, mimicking neural tube development. We investigate how biochemical features of Shh and Shh-interacting proteins affect patterning length scales. By measuring clearance rates, we determine that Shh has an extracellular half-life below 1.5 h, substantially shorter than downstream gene expression dynamics, indicating gradients are continually renewed during patterning. We provide evidence that progenitor identity acquisition and maintenance depend on both Shh concentration and exposure duration. Together, this approach provides a quantitative framework for investigating morphogen patterning, enabling reproducible control of morphogen dynamics to dissect the interplay between biochemical cues, gradient formation biophysics, and transcriptional programs underlying developmental patterning.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"18 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900561","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

Single-cell transcriptomic analysis highlights specific cell types manipulated by Fusarium head blight fungus leading to wheat susceptibility 单细胞转录组学分析强调了小麦对赤霉病的敏感性

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-21 DOI: 10.1016/j.devcel.2025.07.022

Wan-Qian Wei, Shuang Li, Dong Zhang, Wei-Hua Tang

{"title":"Single-cell transcriptomic analysis highlights specific cell types manipulated by Fusarium head blight fungus leading to wheat susceptibility","authors":"Wan-Qian Wei, Shuang Li, Dong Zhang, Wei-Hua Tang","doi":"10.1016/j.devcel.2025.07.022","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.022","url":null,"abstract":"Most invading fungi can be recognized by the plant immune system and trigger host defenses, but adapted pathogens can cause susceptibility. Multicellular plants might use cell-differentiated strategies to restrict non-adapted fungi invasion and to yield adapted fungi colonization. Here, we employed single-cell RNA sequencing (scRNA-seq) to identify the responses of wheat coleoptiles to the adapted Fusarium graminearum (Fgr) and the non-adapted Fusarium oxysporum f. sp. cubense (Foc) at 1, 2, and 3 days post inoculation. We profiled the transcriptomes of over 90,000 cells and identified cell-type-specific responses of eight major cell types: stomata, epidermis, chlorenchyma, parenchyma, outer sheath, inner sheath, phloem, and procambium. Differential expression analyses indicated that the upregulation of immune pathways was compartmentalized in nonhost resistance to Foc but widespread in susceptible interaction with Fgr. Pseudotime analyses showed continuous state transitions of mesophyll cells along disease progression and that Fgr induces a state of low transcriptional activity in chlorenchyma cells.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"22 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900418","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

StBPA1 attenuates surface receptor activation and finely regulates immune responses against bacterial and oomycete pathogens in potato StBPA1可减弱马铃薯表面受体的激活并精细调节对细菌和卵菌病原体的免疫反应

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-20 DOI: 10.1016/j.devcel.2025.07.021

Jie Li, Aifang Ma, Jiahan Ying, Xiuli Qin, Wenjie Liu, Wenjing Cui, Zhengyu Chen, Dongli Wang, Dongqin Chen, Zhiyuan Yin, Maofeng Jing, Guangyuan Xu, Ingo Hein, Xiangxiu Liang, Paul R.J. Birch, Daolong Dou, Xiaodan Wang

{"title":"StBPA1 attenuates surface receptor activation and finely regulates immune responses against bacterial and oomycete pathogens in potato","authors":"Jie Li, Aifang Ma, Jiahan Ying, Xiuli Qin, Wenjie Liu, Wenjing Cui, Zhengyu Chen, Dongli Wang, Dongqin Chen, Zhiyuan Yin, Maofeng Jing, Guangyuan Xu, Ingo Hein, Xiangxiu Liang, Paul R.J. Birch, Daolong Dou, Xiaodan Wang","doi":"10.1016/j.devcel.2025.07.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.021","url":null,"abstract":"Plants utilize plasma-membrane-localized pattern recognition receptors (PRRs) to sense and respond to microbial infections. The downstream regulatory components have been studied extensively, but the mechanisms ensuring appropriate immune responses to diverse pathogens remain enigmatic. We report that a core regulatory component named StBPA1 (BINDING PARTNER OF ACD11) is a molecular switch that controls both anti-bacterial and anti-oomycete immunity. <ce:italic>StBPA1-</ce:italic>knockout displays dwarfed growth, enhanced pattern-triggered immunity (PTI), and broad-spectrum resistance to potato bacterial wilt and late blight diseases. StBPA1 negatively regulates the FLAGELLIN SENSING 2 (StFLS2)-BRI1-ASSOCIATED KINASE 1 (StBAK1)/SUPPRESSOR OF BIR1-1 (StSOBIR1)-StBAK1 immune complex formation and inhibits StFLS2 kinase activity to prevent constitutive immune responses. In turn, StBAK1 specifically phosphorylates StBPA1 at Thr<ce:sup loc=\"post\">193</ce:sup>/Ser<ce:sup loc=\"post\">195</ce:sup>. This modification is enhanced by flg22/INF1 perception and impairs the negative regulatory role of StBPA1, thereby ensuring proper immune signaling. These findings identify an StBPA1-PRR complex regulatory module and highlight inhibitions by StBPA1 as key mechanisms to ensure efficient yet strictly regulated immune responses against different pathogens.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"15 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900505","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

Enhancer remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm OTX2的增强子重塑指导哺乳动物终末内胚层的规范和模式

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-19 DOI: 10.1016/j.devcel.2025.07.020

Ly-sha Ee, Daniel Medina-Cano, Emily Goetzler, Christopher Uyehara, Clayton Schwarz, Eralda Salataj, Subhashini Madhuranath, Todd Evans, Anna-Katerina Hadjantonakis, Effie Apostolou, Alexander Polyzos, Thomas Vierbuchen, Matthias Stadtfeld

{"title":"Enhancer remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm","authors":"Ly-sha Ee, Daniel Medina-Cano, Emily Goetzler, Christopher Uyehara, Clayton Schwarz, Eralda Salataj, Subhashini Madhuranath, Todd Evans, Anna-Katerina Hadjantonakis, Effie Apostolou, Alexander Polyzos, Thomas Vierbuchen, Matthias Stadtfeld","doi":"10.1016/j.devcel.2025.07.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.020","url":null,"abstract":"The molecular mechanisms that drive essential patterning events in the mammalian embryo remain poorly understood. Analysis of transcription factor expression kinetics at peri-gastrulation stages of development suggest Otx2 as a candidate regulator of the definitive endoderm, the precursor of all gut-derived organs. Accordingly, timed OTX2 depletion in gastruloids or during directed differentiation results in abnormal definitive endoderm specification in mouse and human, characterized by altered expression of components and transcriptional targets of the canonical WNT signaling pathway, perturbed adhesion and migration programs, and de-repression of regulators of other lineages. These defects cumulate in impaired foregut formation. Mechanistically, OTX2 is required to activate a subset of endoderm-specific enhancers and to suppress select enhancers of other lineages, allowing timely exit from the primitive streak and correct specification of anterior endoderm. Our results establish OTX2 as an early gut regulator and suggest molecular principles underlying spatiotemporal cell identity conserved across germ layers and species.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"16 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900506","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

S-nitrosylation coordinates stomatal development and functions. s -亚硝基化协调气孔发育和功能。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-08-18 DOI: 10.1016/j.devcel.2025.07.017

Christine Helen Foyer

引用次数: 0