Developmental cellPub Date : 2025-09-09DOI: 10.1016/j.devcel.2025.08.009
Oliver C K Inge, Elias Copin, Jake Cornwall-Scoones, Borzo Gharibi, Irene Rodriguez-Hernandez, Pablo Soro-Barrio, Molly Strom, Probir Chakravarty, James Briscoe, Silvia D M Santos
{"title":"Combinatorial BMP4 and activin direct the choice between alternate routes to endoderm in a stem cell model of human gastrulation.","authors":"Oliver C K Inge, Elias Copin, Jake Cornwall-Scoones, Borzo Gharibi, Irene Rodriguez-Hernandez, Pablo Soro-Barrio, Molly Strom, Probir Chakravarty, James Briscoe, Silvia D M Santos","doi":"10.1016/j.devcel.2025.08.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.009","url":null,"abstract":"<p><p>Lineage specification requires accurate interpretation of multiple signaling cues. However, how combinatorial signaling histories influence fate outcomes remains unclear. We combined single-cell transcriptomics, live-cell imaging, and mathematical modeling to explore how activin and bone morphogenetic protein 4 (BMP4) guide fate specification during human gastrulation. We see that these signals interact both synergistically and antagonistically to drive fate decisions. We find that definitive endoderm arises from lineage convergence: a direct route from pluripotency and an indirect route via a mesoderm progenitor state. Cells pass through temporal windows of signaling competency, and the relative concentration of activin and BMP4 dictates the trajectory choice. The efficiency between routes is underpinned by a dual role of BMP4 in inducing mesoderm genes while promoting pluripotency exit. This work underscores that the combination of signals a cell is exposed to not only directs its final fate but also the developmental route taken, suggesting lineage convergence enhances robustness in fate specification.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032966","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}
{"title":"A pathological role of O-GlcNAcylation-driven TR11B production and function in lung adenocarcinoma","authors":"Shiyu Qiu, Lifang Ma, Keke Yu, Xin Xu, Xiao Zhang, Wenjun Yu, Kai Wang, Xiaoting Tian, Yayou Miao, Yikun Wang, Wanxin Guo, Xiangfei Xue, Jiangtao Cui, Xuewen Yu, Rui Kang, Qianjun Zhou, Yongchun Yu, Daolin Tang, Jiayi Wang","doi":"10.1016/j.devcel.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.010","url":null,"abstract":"Cytokines link inflammation to tumorigenesis, but the role of post-translational modifications in regulating their function within the extra-tumoral environment remains poorly defined. Here, we identify tumor-derived tumor necrosis factor (TNF) receptor superfamily member 11B (TR11B) as a key driver of lung adenocarcinoma (LUAD) progression and therapeutic resistance. Mechanistically, O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation at serine 151 stabilizes TR11B and facilitates its interaction with the membrane protein EPS15 homology domain-containing protein 1 (EHD1), promoting cyclin dependent kinase 2 (CDK2) phosphorylation and cell cycle progression. Clinically, elevated O-GlcNAcylated TR11B correlates with advanced LUAD. Genetic deletion of <em>Ogt</em> suppresses tumor development in LUAD mouse models. Importantly, celecoxib, an U.S. Food and Drug Administration (FDA)-approved drug, inhibits O-GlcNAcylation and exerts antitumor effects. These findings reveal a pathological role for cytokine O-GlcNAcylation in LUAD and identify this axis as a potential therapeutic target.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"17 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018073","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 : 2025-09-08DOI: 10.1016/j.devcel.2025.06.023
Yuan Chen
{"title":"SUMOylation of the transcription factor Etv1 in cancer stem cells induces tumorigenesis of non-stem cancer cells","authors":"Yuan Chen","doi":"10.1016/j.devcel.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.023","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Li et al. show that ETS variant transcription factor 1 (Etv1) SUMOylation not only maintains cancer stem cells (CSCs) but also enables their communications with non-CSC cancer cells to induce tumorigenesis of non-CSCs. The finding reveals a new function of CSCs in driving aggressive tumorigenesis that is SUMOylation dependent.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"7 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009318","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 : 2025-09-08DOI: 10.1016/j.devcel.2025.08.008
Ran Lu, Elwira Smakowska-Luzan
{"title":"Novel bacterial strategy to hijack plant immunity through metabolic manipulation","authors":"Ran Lu, Elwira Smakowska-Luzan","doi":"10.1016/j.devcel.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.008","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Yuan et al. explores how the pathogenic bacterium <em>Pseudomonas syringae</em> modulates plant metabolism, particularly through methylglyoxal (MG) accumulation, to suppress immune responses in <em>Arabidopsis</em>. By affecting key proteins TTM2 and CAT2, the pathogen reduces hydrogen peroxide levels, weakening plant defense mechanisms and promoting infection.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"6 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009321","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 : 2025-09-08DOI: 10.1016/j.devcel.2025.06.032
G. Kenneth Gray, Eric G. Carlson, Tatyana Lev, Bailey Marshall, Austin D. Reed, Alex P. Sánchez-Covarrubias, Alecia-Jane Twigger, Aleix Puig-Barbe, Aatish Thennavan, Ayodele Omotoso, Lyndsay M. Murrow, Deeptiman Chatterjee, Siyuan He, Sara Pensa, Brian Aevermann, Norbert K. Tavares, Natalie Chen, Jason A. Hilton, Kerrigan Blake, Yunlong Liu, Walid T. Khaled
{"title":"Defining breast epithelial cell types in the single-cell era","authors":"G. Kenneth Gray, Eric G. Carlson, Tatyana Lev, Bailey Marshall, Austin D. Reed, Alex P. Sánchez-Covarrubias, Alecia-Jane Twigger, Aleix Puig-Barbe, Aatish Thennavan, Ayodele Omotoso, Lyndsay M. Murrow, Deeptiman Chatterjee, Siyuan He, Sara Pensa, Brian Aevermann, Norbert K. Tavares, Natalie Chen, Jason A. Hilton, Kerrigan Blake, Yunlong Liu, Walid T. Khaled","doi":"10.1016/j.devcel.2025.06.032","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.032","url":null,"abstract":"Single-cell studies on breast tissue have contributed to a change in our understanding of breast epithelial diversity that has, in turn, precipitated a lack of consensus on breast cell types. The confusion surrounding this issue highlights a possible challenge for advancing breast atlas efforts. In this perspective, we present our consensus on the identities, properties, and naming conventions for breast epithelial cell types and propose goals for future atlas endeavors. Our proposals and their underlying thought processes aim to catalyze the adoption of a shared model for this tissue and to serve as guidance for other investigators facing similar challenges.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"27 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009320","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 : 2025-09-08DOI: 10.1016/j.devcel.2025.06.010
Lisa B. Earnest-Noble, Bradley J. Goldstein
{"title":"A bridge too far: Identification of bridge cell states as drivers of plasticity in neuroblastoma","authors":"Lisa B. Earnest-Noble, Bradley J. Goldstein","doi":"10.1016/j.devcel.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.010","url":null,"abstract":"Understanding tumor cell plasticity, a potential mechanism driving therapeutic resistance in many cancers, represents a key oncologic challenge. In this issue of <em>Developmental Cell</em>, Xu et al. leverage neuroblastoma as a tractable model for exploring mechanisms of tumor plasticity and provide key insights into drivers of tumor cell states.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"132 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009319","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 : 2025-09-05DOI: 10.1016/j.devcel.2025.08.014
Xiangyi Ke, Benjamin van Soldt, Lukas Vlahos, Yizhuo Zhou, Jun Qian, Pasquale Laise, Joel George, Claudia Capdevila, Ian Glass, Kelley Yan, Andrea Califano, Wellington V. Cardoso
{"title":"Morphogenesis and regeneration share a conserved core transition cell state program that controls lung epithelial cell fate","authors":"Xiangyi Ke, Benjamin van Soldt, Lukas Vlahos, Yizhuo Zhou, Jun Qian, Pasquale Laise, Joel George, Claudia Capdevila, Ian Glass, Kelley Yan, Andrea Califano, Wellington V. Cardoso","doi":"10.1016/j.devcel.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.014","url":null,"abstract":"(Developmental Cell <em>60</em>, 819–836.e1–e7; March 24, 2025)","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"16 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996038","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 : 2025-09-02DOI: 10.1016/j.devcel.2025.08.005
Yumiko K. Kawamura, Evgeniy A. Ozonov, Panagiotis Papasaikas, Takashi Kondo, Nhuong V. Nguyen, Michael B. Stadler, Sebastien A. Smallwood, Haruhiko Koseki, Antoine H.F.M. Peters
{"title":"Preventing CpG hypermethylation in oocytes safeguards mouse development","authors":"Yumiko K. Kawamura, Evgeniy A. Ozonov, Panagiotis Papasaikas, Takashi Kondo, Nhuong V. Nguyen, Michael B. Stadler, Sebastien A. Smallwood, Haruhiko Koseki, Antoine H.F.M. Peters","doi":"10.1016/j.devcel.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.005","url":null,"abstract":"Except for regulatory CpG-island sequences, genomes of most mammalian cells are widely DNA-methylated. In oocytes, though, DNA methylation (DNAme) is largely confined to transcribed regions. The mechanisms restricting <em>de novo</em> DNAme in oocytes and their relevance thereof for zygotic genome activation and embryonic development are largely unknown. Here we show that KDM2A and KDM2B, two histone demethylases, prevent genome-wide accumulation of histone H3 lysine 36 di-methylation, thereby impeding DNMT3A-catalyzed DNAme. We demonstrate that aberrant DNAme at CpG islands inherited from <em>Kdm2a/Kdm2b</em> double-mutant oocytes represses gene transcription in two-cell embryos. Aberrant maternal DNAme impairs pre-implantation embryonic development, which is suppressed by <em>Dnmt3a</em> deficiency during oogenesis. Hence, KDM2A/KDM2B are essential for confining the oocyte methylome, thereby conferring competence for early embryonic development. Our research implies that the reprogramming capacity eminent to early embryos is insufficient for erasing aberrant DNAme from maternal chromatin, and that early development is susceptible to gene dosage haplo-insufficiency effects.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"28 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928558","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 : 2025-08-28DOI: 10.1016/j.devcel.2025.08.004
Victoria Jorgensen, Min Bao, Sergi Junyent, Christoph M. Häfelfinger, Laura Amaya, Zhaodi Liao, Brian A. Williams, Dong-Yuan Chen, Amanda Wu, Matt Thomson, Magdalena Zernicka-Goetz
{"title":"Efficient stem cell-derived mouse embryo models for environmental studies","authors":"Victoria Jorgensen, Min Bao, Sergi Junyent, Christoph M. Häfelfinger, Laura Amaya, Zhaodi Liao, Brian A. Williams, Dong-Yuan Chen, Amanda Wu, Matt Thomson, Magdalena Zernicka-Goetz","doi":"10.1016/j.devcel.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.004","url":null,"abstract":"Blastoids are stem cell-derived structures that mimic natural blastocysts by incorporating all three lineages: trophectoderm, epiblast, and primitive endoderm. However, current methods often yield incomplete structures that fail to cavitate or to form a proper primitive endoderm. To overcome these limitations, we develop a modular approach by aggregating three murine stem cell types: embryonic stem cells (ESCs), ESCs with inducible GATA4 expression (iG4-ESCs), and trophoblast stem cells (TSCs). This method yields cavitated blastocyst-like structures—termed iG4-blastoids—with approximately 80% efficiency. Single-cell RNA sequencing confirms their close resemblance to mature mouse blastocysts. Notably, culturing iG4-blastoids without FGF4 enhances specification of the invasive mural trophectoderm, and approximately 12% of structures undergo post-implantation-like morphogenesis <em>in vitro</em>. Using this model, we show that caffeine, alcohol, nicotine, and amino acid variations affect iG4-blastoids and natural embryos similarly, underscoring their utility as a robust model for investigating the impact of diverse environmental factors on embryogenesis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"52 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911213","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}