Pub Date : 2025-12-01DOI: 10.1016/j.devcel.2025.10.009
Jie Zhao, Mingjia Chen
Flowering plants have complex mechanisms that perceive ambient temperature and fine-tune flowering time. In this issue of Developmental Cell, Wu et al. reveal a mechanism of thermosensory regulation of flowering mediated by NAT10s-dependent N4-acetylcytidine modification of FLOWERING LOCUS M (FLM) transcripts to control differential alternative splicing of FLM.
{"title":"How to blossom in the cold: An mRNA acetylation-mediated regulatory switch in plants","authors":"Jie Zhao, Mingjia Chen","doi":"10.1016/j.devcel.2025.10.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.009","url":null,"abstract":"Flowering plants have complex mechanisms that perceive ambient temperature and fine-tune flowering time. In this issue of <em>Developmental Cell</em>, Wu et al. reveal a mechanism of thermosensory regulation of flowering mediated by NAT10s-dependent <em>N</em><sup>4</sup>-acetylcytidine modification of <em>FLOWERING LOCUS M</em> (<em>FLM</em>) transcripts to control differential alternative splicing of <em>FLM</em>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"6 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651037","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}
Pub Date : 2025-12-01DOI: 10.1016/j.devcel.2025.11.001
Víctor Sánchez de Medina Hernández, Marintia M. Nava-García, Anita Bianchi, Marion Clavel, Ranjith K. Papareddy, Lina Benchalel, Veselin I. Andreev, Varsha Mathur, Azadeh Mohseni, Marta García-León, Peng Gao, Juan Carlos de la Concepción, Lorenzo Picchianti, Nenad Grujic, Roksolana Kobylinska, Alibek Abdrakhmanov, Héloïse Duvergé, Gaurav Anand, Nils Leibrock, Juncai Ma, Margot Raffeiner, Timothy Scott Crawford, Luca Argirò, Mateusz Matuszkiewicz, Cheuk-Ling Wun, Jakob Valdbjørn Kanne, Anton Meinhart, Elisabeth Roitinger, Isabel Bäurle, Byung Ho Kang, Morten Petersen, Suayib Üstün, Yogesh Kulathu, Tim Clausen, Silvia Ramundo, Yasin Dagdas
{"title":"Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants","authors":"Víctor Sánchez de Medina Hernández, Marintia M. Nava-García, Anita Bianchi, Marion Clavel, Ranjith K. Papareddy, Lina Benchalel, Veselin I. Andreev, Varsha Mathur, Azadeh Mohseni, Marta García-León, Peng Gao, Juan Carlos de la Concepción, Lorenzo Picchianti, Nenad Grujic, Roksolana Kobylinska, Alibek Abdrakhmanov, Héloïse Duvergé, Gaurav Anand, Nils Leibrock, Juncai Ma, Margot Raffeiner, Timothy Scott Crawford, Luca Argirò, Mateusz Matuszkiewicz, Cheuk-Ling Wun, Jakob Valdbjørn Kanne, Anton Meinhart, Elisabeth Roitinger, Isabel Bäurle, Byung Ho Kang, Morten Petersen, Suayib Üstün, Yogesh Kulathu, Tim Clausen, Silvia Ramundo, Yasin Dagdas","doi":"10.1016/j.devcel.2025.11.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.11.001","url":null,"abstract":"","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"132 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657128","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}
Pub Date : 2025-11-27DOI: 10.1016/j.devcel.2025.10.018
Jamie Zagozewski, Parthiv Haldipur, Kathleen J. Millen, Tamra E. Werbowetski-Ogilvie
Over the last decade, an unprecedented number of sequencing studies have characterized the molecular landscape of pediatric brain cancers, including the highly heterogeneous tumor medulloblastoma (MB). Extensive MB profiling has enabled a much deeper understanding of the primitive neurodevelopmental programs that are hijacked during tumor progression. However, we have yet to successfully target and fully eradicate the putative stem and early progenitor cells that drive MB tumorigenesis. This goal will require better human models that faithfully recapitulate oncogenic events, a deeper understanding of the mechanisms governing cell fate decisions in the primary and metastatic compartments, and comprehensive validation studies of MB stem/progenitor cell molecular signatures extracted from bioinformatics datasets. In this perspective, we summarize the current knowledge of the developmental origins of MB and highlight the unmet needs pertaining to tumor modeling, characterization of molecular programs driving metastatic cells, and post-transcriptional regulation of cell fate.
{"title":"Medulloblastoma stem cell programs: Molecular roadmaps of disease progression","authors":"Jamie Zagozewski, Parthiv Haldipur, Kathleen J. Millen, Tamra E. Werbowetski-Ogilvie","doi":"10.1016/j.devcel.2025.10.018","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.018","url":null,"abstract":"Over the last decade, an unprecedented number of sequencing studies have characterized the molecular landscape of pediatric brain cancers, including the highly heterogeneous tumor medulloblastoma (MB). Extensive MB profiling has enabled a much deeper understanding of the primitive neurodevelopmental programs that are hijacked during tumor progression. However, we have yet to successfully target and fully eradicate the putative stem and early progenitor cells that drive MB tumorigenesis. This goal will require better human models that faithfully recapitulate oncogenic events, a deeper understanding of the mechanisms governing cell fate decisions in the primary and metastatic compartments, and comprehensive validation studies of MB stem/progenitor cell molecular signatures extracted from bioinformatics datasets. In this perspective, we summarize the current knowledge of the developmental origins of MB and highlight the unmet needs pertaining to tumor modeling, characterization of molecular programs driving metastatic cells, and post-transcriptional regulation of cell fate.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"175 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609719","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}
Pub Date : 2025-11-27DOI: 10.1016/j.devcel.2025.10.017
Jun Wu, Gen Li, Jiawen Zhou, Xuan Sun, Haoyu Wang, Haipeng Gong, Peng Jiang
{"title":"Vitamin B6 preserves the stemness-like phenotypes and antitumor ability of CD8+ T cells","authors":"Jun Wu, Gen Li, Jiawen Zhou, Xuan Sun, Haoyu Wang, Haipeng Gong, Peng Jiang","doi":"10.1016/j.devcel.2025.10.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.017","url":null,"abstract":"","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609203","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}
Pub Date : 2025-11-27DOI: 10.1016/j.devcel.2025.10.019
Xiaoyan Sun, Shanshan Che, Hengchao Wang, Yanling Fan, Yingjie Ding, Ansheng Tan, Kuan Yang, Jianli Hu, Yixin Zhang, Miyang Ma, Jinghao Hu, Shuhui Sun, Shuai Ma, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu
Vascular aging is a key driver of cardiovascular disease, yet models capturing its complexity in humans are lacking. Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disorder caused by the LMNA mutation, provides a model to study accelerated vascular decline. Here, we developed a blood vessel organoid (BVO) model from HGPS-mutant human embryonic stem cells (hESCs). These BVOs model HGPS vascular defects and reveal significant downregulation of serum response factor (SRF), a trend also observed in the vasculature of naturally aged primates. We show that SRF regulates angiogenesis-related genes, and that its overexpression rescues endothelial function in HGPS organoids. In summary, we establish a 3D human organoid model of vascular aging, identify SRF as a pivotal regulator and provide a powerful platform for discovering geroprotective therapies.
{"title":"Vascular organoid model of Hutchinson-Gilford progeria syndrome uncovers repression of the SRF pathway in premature aging","authors":"Xiaoyan Sun, Shanshan Che, Hengchao Wang, Yanling Fan, Yingjie Ding, Ansheng Tan, Kuan Yang, Jianli Hu, Yixin Zhang, Miyang Ma, Jinghao Hu, Shuhui Sun, Shuai Ma, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu","doi":"10.1016/j.devcel.2025.10.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.019","url":null,"abstract":"Vascular aging is a key driver of cardiovascular disease, yet models capturing its complexity in humans are lacking. Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disorder caused by the <em>LMNA</em> mutation, provides a model to study accelerated vascular decline. Here, we developed a blood vessel organoid (BVO) model from HGPS-mutant human embryonic stem cells (hESCs). These BVOs model HGPS vascular defects and reveal significant downregulation of serum response factor (SRF), a trend also observed in the vasculature of naturally aged primates. We show that SRF regulates angiogenesis-related genes, and that its overexpression rescues endothelial function in HGPS organoids. In summary, we establish a 3D human organoid model of vascular aging, identify SRF as a pivotal regulator and provide a powerful platform for discovering geroprotective therapies.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"19 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609721","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}
Pub Date : 2025-11-20DOI: 10.1016/j.devcel.2025.10.014
Atsuhiro Taguchi, Alexandre P. Magalhães, Adriano Bolondi, Ming-Kang Lee, Helene Kretzmer, Lars Wittler, Denes Hnisz, Alexander Meissner
The maturation of lineage-committed embryonic hepatocytes requires both the timed activation of metabolic gene regulatory networks (GRNs) and silencing of embryonic programs to achieve adult hepatic functions. However, in vitro derivation of mature hepatocytes remains imperfect, and key transcriptional regulators governing GRN rewiring during late development are still insufficiently defined. To address this, we generated a developmental reference atlas and employed a dCas9 activation screen with single-cell transcriptomics on primary mouse embryonic hepatocytes, enabling effect ranking among late-onset transcription regulators. We identify Nr1i3 as a potent inducer of pericentrally expressed metabolic genes and Nfix as a critical suppressor of embryonic and periportal signatures. Supplementing liver zonation patterning signals with these regulators further enhanced the expression of pericentrally zonated metabolic genes, emphasizing the importance of a microenvironment-targeted approach. Our screening and analysis therefore highlight regulatory mechanisms underlying organ maturation and offer general strategies for improving the functionality of in vitro-derived cells.
{"title":"Single-cell activation screen identifies hepatic maturation regulators with zonal resolution","authors":"Atsuhiro Taguchi, Alexandre P. Magalhães, Adriano Bolondi, Ming-Kang Lee, Helene Kretzmer, Lars Wittler, Denes Hnisz, Alexander Meissner","doi":"10.1016/j.devcel.2025.10.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.014","url":null,"abstract":"The maturation of lineage-committed embryonic hepatocytes requires both the timed activation of metabolic gene regulatory networks (GRNs) and silencing of embryonic programs to achieve adult hepatic functions. However, <em>in vitro</em> derivation of mature hepatocytes remains imperfect, and key transcriptional regulators governing GRN rewiring during late development are still insufficiently defined. To address this, we generated a developmental reference atlas and employed a dCas9 activation screen with single-cell transcriptomics on primary mouse embryonic hepatocytes, enabling effect ranking among late-onset transcription regulators. We identify <em>Nr1i3</em> as a potent inducer of pericentrally expressed metabolic genes and <em>Nfix</em> as a critical suppressor of embryonic and periportal signatures. Supplementing liver zonation patterning signals with these regulators further enhanced the expression of pericentrally zonated metabolic genes, emphasizing the importance of a microenvironment-targeted approach. Our screening and analysis therefore highlight regulatory mechanisms underlying organ maturation and offer general strategies for improving the functionality of <em>in vitro</em>-derived cells.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"38 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554860","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}
Pub Date : 2025-11-20DOI: 10.1016/j.devcel.2025.10.015
Jingbo Sun, Irem Sude Atiş, Stéfany L.L. Empke, Mustafa K. Khokha, David K. Breslow
Microscopy offers an indispensable technique for visualizing biological processes and for defining cytological abnormalities characteristic of disease. However, combining microscopy with the power of pooled CRISPR screening presents considerable technical challenges, hindering application of systematic genetic analysis to imaging-defined phenotypes. Here, we establish a fluorescence microscopy-based CRISPR screening platform that combines ease of implementation with flexible analysis of live-cell or antibody-based molecular markers, including post-translational modifications. Applying this methodology, we systematically identify regulators of primary cilium structure and function in human cells through targeted and genome-wide screens. We further show that integration of screens focused on distinct ciliary phenotypes yields multi-dimensional profiles that delineate precise gene functions. Among the identified hits, TZMP1 (SMIM27) encodes a microprotein at the ciliary transition zone that is required for ciliogenesis in human cells and for ciliary function in Xenopus embryos. More broadly, our approach provides a technological and conceptual strategy for microscopy-based functional genomics.
{"title":"A microscopy-based CRISPR screening platform enables organellar functional genomics and illuminates ciliary biology","authors":"Jingbo Sun, Irem Sude Atiş, Stéfany L.L. Empke, Mustafa K. Khokha, David K. Breslow","doi":"10.1016/j.devcel.2025.10.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.015","url":null,"abstract":"Microscopy offers an indispensable technique for visualizing biological processes and for defining cytological abnormalities characteristic of disease. However, combining microscopy with the power of pooled CRISPR screening presents considerable technical challenges, hindering application of systematic genetic analysis to imaging-defined phenotypes. Here, we establish a fluorescence microscopy-based CRISPR screening platform that combines ease of implementation with flexible analysis of live-cell or antibody-based molecular markers, including post-translational modifications. Applying this methodology, we systematically identify regulators of primary cilium structure and function in human cells through targeted and genome-wide screens. We further show that integration of screens focused on distinct ciliary phenotypes yields multi-dimensional profiles that delineate precise gene functions. Among the identified hits, <em>TZMP1</em> (<em>SMIM27</em>) encodes a microprotein at the ciliary transition zone that is required for ciliogenesis in human cells and for ciliary function in <em>Xenopus</em> embryos. More broadly, our approach provides a technological and conceptual strategy for microscopy-based functional genomics.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"12 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554809","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}
Pub Date : 2025-11-17DOI: 10.1016/j.devcel.2025.10.013
Andrew Neumann, Rytis Prekeris
In this issue of Developmental Cell, Jӓntti et al. identify the unique localization of EPLINα isoform to Rab21-positive endosomes, where it is necessary for the recycling of β1-integrin. They then provide insights into EPLINα′s role in cell-to-matrix adhesion, cell migration, and cancer progression.
{"title":"Checking in with EPLIN: EPLINα as a regulator of integrin trafficking","authors":"Andrew Neumann, Rytis Prekeris","doi":"10.1016/j.devcel.2025.10.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.013","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Jӓntti et al. identify the unique localization of EPLINα isoform to Rab21-positive endosomes, where it is necessary for the recycling of β1-integrin. They then provide insights into EPLINα′s role in cell-to-matrix adhesion, cell migration, and cancer progression.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531505","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}
Pub Date : 2025-11-17DOI: 10.1016/j.devcel.2025.10.001
Víctor Herrera-Fernández, Markus Hengstschläger, Alexis J. Lomakin
Cells in motion must adapt their migratory strategies to diverse environmental stresses. In this issue of Developmental Cell, Yu et al. identify an evolutionarily conserved, switch-like phenotypic transition to inchworm migration in amoeboid cells encountering super-sticky microenvironments.
{"title":"Ameboid cell inchworming: An adaptive phenotype triggered by abiotic-like stress","authors":"Víctor Herrera-Fernández, Markus Hengstschläger, Alexis J. Lomakin","doi":"10.1016/j.devcel.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.001","url":null,"abstract":"Cells in motion must adapt their migratory strategies to diverse environmental stresses. In this issue of <em>Developmental Cell</em>, Yu et al. identify an evolutionarily conserved, switch-like phenotypic transition to inchworm migration in amoeboid cells encountering super-sticky microenvironments.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"60 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531503","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}
Pub Date : 2025-11-17DOI: 10.1016/j.devcel.2025.10.008
Janny Pineiro-Llanes, Mashael F. Aldossari, Rodrigo Cristofoletti
Intestinal organoid culture has widely depended on exogenous laminin-rich matrices to provide a supportive environment for organoid development. In this issue of Developmental Cell, Chrisnandy and Lütolf now report that human and mouse intestinal epithelial cells can secrete their own basement membrane, enabling organoid formation even without exogenous laminin.
{"title":"Epithelial-derived basement membranes help orchestrate crypt-villus patterning in vitro","authors":"Janny Pineiro-Llanes, Mashael F. Aldossari, Rodrigo Cristofoletti","doi":"10.1016/j.devcel.2025.10.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.10.008","url":null,"abstract":"Intestinal organoid culture has widely depended on exogenous laminin-rich matrices to provide a supportive environment for organoid development. In this issue of <em>Developmental Cell</em>, Chrisnandy and Lütolf now report that human and mouse intestinal epithelial cells can secrete their own basement membrane, enabling organoid formation even without exogenous laminin.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531504","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：