Developmental cellPub Date : 2026-06-10DOI: 10.1016/j.devcel.2026.05.009
Albert Zhang, Jonah R Chan
{"title":"Right on cue-Neuronal signals guide myelination in the developing cortex.","authors":"Albert Zhang, Jonah R Chan","doi":"10.1016/j.devcel.2026.05.009","DOIUrl":"10.1016/j.devcel.2026.05.009","url":null,"abstract":"<p><p>Myelinated and unmyelinated axons are detected throughout the central nervous system (CNS), suggesting that axonal signals influence myelination. In this issue of Developmental Cell, Domínguez-Iturza et al.<sup>1</sup> generated a library of axonal signals and identified candidate pro-myelinating molecules that could shape myelination patterns in the developing cortex.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"61 6","pages":"1172-1173"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216471","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-05-19DOI: 10.1016/j.devcel.2026.04.012
Xian Zhang, Wilfred Wong, Hyein S Cho, Dapeng Yang, Gary Dixon, Renhe Luo, Dingyu Liu, Denis Torre, Shigeaki Umeda, Federico González, Gokce Askan, Aslihan Yavas, Jeyaram Ravichandran Damodaran, Robert W Rickert, Rajya Kappagantula, Fong Cheng Pan, Victoria G Aveson, Adrien Grimont, William B Fall, Xianming Wang, Julian Pulecio, Samuel J Kaplan, Heng Pan, Xianlu Laura Peng, Jen Jen Yeh, Steven D Leach, Christine A Iacobuzio-Donahue, Rohit Chandwani, Christina S Leslie, Danwei Huangfu
{"title":"Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation.","authors":"Xian Zhang, Wilfred Wong, Hyein S Cho, Dapeng Yang, Gary Dixon, Renhe Luo, Dingyu Liu, Denis Torre, Shigeaki Umeda, Federico González, Gokce Askan, Aslihan Yavas, Jeyaram Ravichandran Damodaran, Robert W Rickert, Rajya Kappagantula, Fong Cheng Pan, Victoria G Aveson, Adrien Grimont, William B Fall, Xianming Wang, Julian Pulecio, Samuel J Kaplan, Heng Pan, Xianlu Laura Peng, Jen Jen Yeh, Steven D Leach, Christine A Iacobuzio-Donahue, Rohit Chandwani, Christina S Leslie, Danwei Huangfu","doi":"10.1016/j.devcel.2026.04.012","DOIUrl":"10.1016/j.devcel.2026.04.012","url":null,"abstract":"<p><p>The lack of accurate human models that recapitulate pancreatic ductal adenocarcinoma (PDAC) initiation has hindered therapeutic development. Using pluripotent stem cell-derived pancreatic progenitor organoids, we established a human PDAC model that faithfully reproduces the genetic, epigenetic, and transcriptomic trajectories of tumor initiation and progression, validated against clinical datasets and tumor histopathology. We demonstrate that CDKN2A loss, which is nearly universal in patients but dispensable in mouse models, is essential for neoplastic transformation when combined with KRAS and TP53 mutations, whereas SMAD4 loss promotes tumor progression. Multi-omics profiling reveals epigenetic repression of the pancreatic lineage program during PDAC initiation, alongside AP-1-driven chromatin remodeling. We identify TET1 suppression as a mechanistic link between oncogenic ERK signaling and hypermethylation of essential pancreatic transcription factors. This model captures genetic and epigenetic determinants of human PDAC, reveals antagonism between oncogenic and lineage restriction programs, and supports TET-based lineage restoration as a potential early intervention strategy.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1190-1207.e12"},"PeriodicalIF":9.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981004","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-05-18DOI: 10.1016/j.devcel.2026.04.011
Anna Segú Cristina, Gaëlle Letort, Emeline Perthame, Stéphane Rigaud, David Briand, Aman Kukde, Agata Banach-Latapy, Nick D L Owens, Léo Valon, Jean-Yves Tinevez, Yohanns Bellaïche, Pauline Spéder
{"title":"Adhesion-controlled mechanics of the glial niche regulate neural stem cell proliferative potential.","authors":"Anna Segú Cristina, Gaëlle Letort, Emeline Perthame, Stéphane Rigaud, David Briand, Aman Kukde, Agata Banach-Latapy, Nick D L Owens, Léo Valon, Jean-Yves Tinevez, Yohanns Bellaïche, Pauline Spéder","doi":"10.1016/j.devcel.2026.04.011","DOIUrl":"10.1016/j.devcel.2026.04.011","url":null,"abstract":"<p><p>Stem cell proliferation drives tissue formation and homeostasis. Whether and how niche cell mechanics act in vivo to control this process remains unclear. Here, we identify a triad of cell adhesion molecules from the immunoglobulin superfamily, which physically link neural stem cells (NSCs) to their glial niche in Drosophila. Disrupting this connection increases actomyosin activation and tensile forces in the glial cells, reciprocally causing mechanical stress in NSCs. This promotes lamin accumulation, which causes nuclear deformation and acts as a protective response safeguarding NSC mitosis. However, this response is insufficient, and NSCs display abnormal spindle morphologies and impaired mitotic progression. Ultimately, the loss of NSC and niche mechanical interplay compromises NSC proliferative potential and genome integrity. This study uncovers a fundamental role for niche cell mechanics and members of the immunoglobulin superfamily, acting as mechanoregulators, in controlling stem cell proliferation.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1254-1272.e11"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971339","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}
Developmental cellPub Date : 2026-06-10DOI: 10.1016/j.devcel.2026.05.007
Tianyue Sun, Christoph Scheiermann
{"title":"Dec2 conceals tumors from the immune system.","authors":"Tianyue Sun, Christoph Scheiermann","doi":"10.1016/j.devcel.2026.05.007","DOIUrl":"10.1016/j.devcel.2026.05.007","url":null,"abstract":"<p><p>In this issue of Developmental Cell, Wang et al. establish a murine resectable pancreatic ductal adenocarcinoma (PDAC) model and identify circadian regulator Dec2 as a driver of dormant tumor cells to evade immune surveillance by suppressing antigen presentation. These findings highlight a temporal dimension of tumor immune evasion.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"61 6","pages":"1167-1168"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216316","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}
Developmental cellPub Date : 2026-06-10DOI: 10.1016/j.devcel.2026.05.003
Pauline Vinet, Jean-Marie Frachisse, Sébastien Thomine, Pauline Durand-Smet
{"title":"Sensing forces: How plants convert mechanical cues into biological responses.","authors":"Pauline Vinet, Jean-Marie Frachisse, Sébastien Thomine, Pauline Durand-Smet","doi":"10.1016/j.devcel.2026.05.003","DOIUrl":"10.1016/j.devcel.2026.05.003","url":null,"abstract":"<p><p>Plants encounter mechanical constraints from environmental forces and morphogenesis. Sensing these constraints induces downstream responses that are crucial for plant development and its plasticity in a changing environment. Here, we first provide an overview of the mechanical constraints acting on plants at multiple scales, ranging from organelles to organs. We then focus on the coupling between mechanical stimuli and biological signaling, referred to as mechanotransduction. We highlight distinct modes of coupling, including the sensing of lipid compaction and cell wall status by receptors and channels, as well as the mechanically induced reorganization of cellular components such as the cytoskeleton and plasma membrane. Finally, we discuss the diversity of downstream responses triggered by mechanotransduction and their temporal dynamics. We propose that the diversity of mechanotransduction modalities allows plants to decode mechanical signatures characterized by specific stimulus intensities, durations, and frequencies, thereby eliciting adaptive cellular and developmental responses.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"61 6","pages":"1174-1189"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216920","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-05-11DOI: 10.1016/j.devcel.2026.04.005
Meijuan Xia, Yezi Ma, Yifei Cai, Jingjing Zhao, Yao Zhong, Sibei Guo, Minmin Li, Pei Su, Biao Shen, Huizhen He, Xiaoyuan Chen, Lin Zheng, Le Li, Ziqi Huo, Wen Zhou, Fei Wang, Cuicui Liu, Hongtao Wang, Jiaxi Zhou
{"title":"A machine learning-based megakaryocyte identification system uncovers resident organs, markers, and functional diversity.","authors":"Meijuan Xia, Yezi Ma, Yifei Cai, Jingjing Zhao, Yao Zhong, Sibei Guo, Minmin Li, Pei Su, Biao Shen, Huizhen He, Xiaoyuan Chen, Lin Zheng, Le Li, Ziqi Huo, Wen Zhou, Fei Wang, Cuicui Liu, Hongtao Wang, Jiaxi Zhou","doi":"10.1016/j.devcel.2026.04.005","DOIUrl":"10.1016/j.devcel.2026.04.005","url":null,"abstract":"<p><p>The organ- and stage-specific diversity of megakaryocytes (MKs) has prompted a reassessment of their distribution and functions. By integrating single-cell transcriptomic data across multiple organs and developmental stages, we identified previously unreported MK and platelet markers, including Tnik, a key regulator of MK function and platelet production. Using these markers alongside established ones, we developed a machine learning-based MK identification system (MKIDS) that enables MK detection in the brain, heart, and placenta in mice and humans. Functional studies demonstrated that brain-resident MKs are essential for neural development, underscoring organ-specific roles of MKs in regulating tissue development and function. Transcriptomic integration of MKs across organs and stages, with functional validation, revealed a developmental shift in platelet production-from a mitochondria-low to a mitochondria-enriched subpopulation. Our findings offer a transformative perspective on the MK system, highlighting its cellular diversity, functional complexity, and developmental dynamics.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1319-1339.e8"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927319","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-06-02DOI: 10.1016/j.devcel.2026.05.001
Alexa M Gajda, Mohamed Haloul, Vinay Pai, Keyvan Mollaeian, Khushi J Patel, Raymundo Rodríguez-López, Katie M Beverley, Mark A Sanborn, Kihak Lee, Caitlyn C Castillo, Stephanie M Wilk, Beata M Wolska, Faruk Hossen, Eron N Mendenhall, James C Lee, Irena Levitan, Jalees Rehman, Ekrem Emrah Er
{"title":"Ionic regulation of cancer cell stiffness and metastatic colonization via the MRTFA-KCNMB1 axis.","authors":"Alexa M Gajda, Mohamed Haloul, Vinay Pai, Keyvan Mollaeian, Khushi J Patel, Raymundo Rodríguez-López, Katie M Beverley, Mark A Sanborn, Kihak Lee, Caitlyn C Castillo, Stephanie M Wilk, Beata M Wolska, Faruk Hossen, Eron N Mendenhall, James C Lee, Irena Levitan, Jalees Rehman, Ekrem Emrah Er","doi":"10.1016/j.devcel.2026.05.001","DOIUrl":"10.1016/j.devcel.2026.05.001","url":null,"abstract":"<p><p>Cellular stiffness impacts multiple steps of cancer metastasis, but mechanisms that regulate the stiffness of cancer cells remain poorly understood. Here, we identified potassium efflux and potassium calcium-activated channel subfamily M regulatory beta subunit 1 (KCNMB1), an auxiliary subunit of the large conductance calcium-activated potassium (BK) channels, as regulators of cellular stiffness downstream of myocardin-related transcription factor A (MRTFA). In primary pericytes, KCNMB1 knockdown increased cellular stiffness, which is consistent with the role of potassium efflux in promoting relaxation during excitation-contraction coupling. In a striking contrast, however, KCNMB1 knockdown decreased cancer cells' stiffness. Softer cancer cells were resistant to natural killer (NK) cell mediated cytotoxicity and the low KCNMB1 expression was associated with reduced survival in breast cancer patients. Importantly, pharmacological activation of BK channels reduced metastatic burden in mice and improved lysis of cancer cells by cytotoxic T lymphocytes. These results highlight the ionic regulation of stiffness in cancer cells and point to BK channel agonism as a therapeutic approach.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1223-1237.e7"},"PeriodicalIF":9.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148926","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}
Developmental cellPub Date : 2026-06-10DOI: 10.1016/j.devcel.2026.05.005
David Escobar, Howard C Crawford
{"title":"A human model of progressive pancreatic neoplasia and cancer.","authors":"David Escobar, Howard C Crawford","doi":"10.1016/j.devcel.2026.05.005","DOIUrl":"10.1016/j.devcel.2026.05.005","url":null,"abstract":"<p><p>In this issue of Developmental Cell, Zhang et al.<sup>1</sup> use human pancreatic progenitor organoids to define the tumorigenic threshold governed by mutations in the four most altered genes in PDAC. They connect this transition to AP-1-driven chromatin remodeling, TET1 suppression, and epigenetic restriction of pancreatic lineage programs.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"61 6","pages":"1163-1164"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216262","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-05-21DOI: 10.1016/j.devcel.2026.04.013
Kazunori Yamamoto, Sacha Ichbiah, Matthieu Perez, Joana Borrego-Pinto, Fabrice Delbary, Nathan W Goehring, Paul Northrop, Hervé Turlier, Guillaume Charras
{"title":"Spatiotemporal mapping of the contractile and adhesive forces sculpting early C. elegans embryos.","authors":"Kazunori Yamamoto, Sacha Ichbiah, Matthieu Perez, Joana Borrego-Pinto, Fabrice Delbary, Nathan W Goehring, Paul Northrop, Hervé Turlier, Guillaume Charras","doi":"10.1016/j.devcel.2026.04.013","DOIUrl":"10.1016/j.devcel.2026.04.013","url":null,"abstract":"<p><p>Embryo shape is determined by cell mechanics, intercellular interactions, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging because temporal changes in tension are unknown. Here, we characterize the spatiotemporal changes in cellular tensions shaping early nematode embryos using atomic force microscopy (AFM), live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that temporally calibrates relative inferred tensions using cortical myosin enrichment and absolute tensions obtained by AFM. Applying this approach to embryos within their native shell provides a spatiotemporal map of absolute tensions. This reveals that ABa, ABp, and EMS compaction is driven by increased cell-medium tension, whereas P<sub>2</sub>'s initial exclusion is due to high cell-cell contact tension. We further uncover a direct contribution of cadherins to cell-cell contact tension, comparable in magnitude to cadherins' indirect contribution via actomyosin regulation.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1273-1288.e4"},"PeriodicalIF":8.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986945","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}
Developmental cellPub Date : 2026-06-10Epub Date: 2026-04-28DOI: 10.1016/j.devcel.2026.04.001
Lan Wang, Chris R Harris, Crissy Dudgeon, Orjola Prela, Juliana Cazarin, Ching-Hua Shih, Christina Davidson, Anthony Casabianca, Subhajyoti De, Wade Narrow, Jennifer Becker, Paul M Grandgenett, Michael A Hollingsworth, Jean L Grem, Minsoo Kim, Yeonsun Hong, Scott Gerber, Paula M Vertino, Chongfeng Gao, Zachary Klamer, Anna Repesh, Yansheng Hao, Allison T Ryan, Mitchell Breitenbach, Anna Bianchi, Jashodeep Datta, Brian J Altman, Brian Haab, Darren R Carpizo
{"title":"The circadian gene Dec2 promotes pancreatic cancer progression and dormancy through immune evasion.","authors":"Lan Wang, Chris R Harris, Crissy Dudgeon, Orjola Prela, Juliana Cazarin, Ching-Hua Shih, Christina Davidson, Anthony Casabianca, Subhajyoti De, Wade Narrow, Jennifer Becker, Paul M Grandgenett, Michael A Hollingsworth, Jean L Grem, Minsoo Kim, Yeonsun Hong, Scott Gerber, Paula M Vertino, Chongfeng Gao, Zachary Klamer, Anna Repesh, Yansheng Hao, Allison T Ryan, Mitchell Breitenbach, Anna Bianchi, Jashodeep Datta, Brian J Altman, Brian Haab, Darren R Carpizo","doi":"10.1016/j.devcel.2026.04.001","DOIUrl":"10.1016/j.devcel.2026.04.001","url":null,"abstract":"<p><p>The mechanisms that regulate immune evasion by pancreatic ductal adenocarcinomas (PDACs) remain poorly understood. Using a mouse model of resectable PDAC, we identified an unknown role of the circadian rhythm gene Differentially Expressed in Chondrocytes 2 (Dec2) in regulating tumor progression and dormancy. Deletion of Dec2 from tumor cells substantially increased mouse survival after resection due to an immune-mediated mechanism, as the survival benefit was abrogated under immunodeficient conditions. Dec2 promotes immune evasion by repressing major histocompatibility complex class I (MHC-I)-dependent antigen presentation and by repolarizing the tumor microenvironment from immunologically cold (low T cell infiltration) to hot (elevated T cell infiltration). Dec2 is also a regulator of circadian rhythms, and we found that genes involved in MHC-I antigen presentation and MHC-I surface localization oscillated in a circadian manner, which was lost upon deletion of Dec2 in vitro. We conclude that Dec2 promotes primary PDAC progression and likely metastatic dormancy through immune evasion.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":"1208-1222.e9"},"PeriodicalIF":9.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765530","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}