Developmental cellPub Date : 2025-03-26DOI: 10.1016/j.devcel.2025.03.001
Rory Osborne, Anne-Marie Labandera, Alex J. Ryder, Anastasia Kanali, Tianyuan Xu, Oluwatunmise Akintewe, Maximillian A. Schwarze, Christian D. Morgan, Sjon Hartman, Eirini Kaiserli, Daniel J. Gibbs
{"title":"VRN2-PRC2 facilitates light-triggered repression of PIF signaling to coordinate growth in Arabidopsis","authors":"Rory Osborne, Anne-Marie Labandera, Alex J. Ryder, Anastasia Kanali, Tianyuan Xu, Oluwatunmise Akintewe, Maximillian A. Schwarze, Christian D. Morgan, Sjon Hartman, Eirini Kaiserli, Daniel J. Gibbs","doi":"10.1016/j.devcel.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.001","url":null,"abstract":"VERNALIZATION2 (VRN2) is a flowering plant-specific subunit of the polycomb-repressive complex 2 (PRC2), a conserved eukaryotic holoenzyme that represses gene expression by depositing the histone H3 lysine 27 trimethylation (H3K27me3) mark in chromatin. Previous work established VRN2 as an oxygen-regulated target of the N-degron pathway that may function as a sensor subunit connecting PRC2 activity to the perception of endogenous and environmental cues. Here, we show that VRN2 is enriched in the hypoxic shoot apex and emerging leaves of <em>Arabidopsis</em>, where it negatively regulates growth by establishing a stable and conditionally repressed chromatin state in key PHYTOCHROME INTERACTING FACTOR (PIF)-regulated genes that promote cell expansion. This function is required to keep these genes poised for repression via a light-responsive signaling cascade later in leaf development. Thus, we identify VRN2-PRC2 as a core component of a developmentally and spatially encoded epigenetic mechanism that coordinates plant growth through facilitating the signal-dependent suppression of PIF signaling.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"27 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703190","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 : 2025-03-25DOI: 10.1016/j.devcel.2025.03.002
Xinlu Zhu, Weibing Wang, Simou Sun, Choon-Peng Chng, Yi Xie, Kexin Zhu, Danxia He, Qiyu Liang, Zhiming Ma, Xi Wu, Xuanang Zheng, Weibo Gao, Ali Miserez, Caiji Gao, Jing Yu, Changjin Huang, Jay T. Groves, Yansong Miao
{"title":"Bacterial XopR subverts RIN4 complex-mediated plant immunity via plasma membrane-associated percolation","authors":"Xinlu Zhu, Weibing Wang, Simou Sun, Choon-Peng Chng, Yi Xie, Kexin Zhu, Danxia He, Qiyu Liang, Zhiming Ma, Xi Wu, Xuanang Zheng, Weibo Gao, Ali Miserez, Caiji Gao, Jing Yu, Changjin Huang, Jay T. Groves, Yansong Miao","doi":"10.1016/j.devcel.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.002","url":null,"abstract":"Phytobacteria release type 3 effectors (T3Es) abundant in intrinsically disordered regions (IDRs) to undermine plant defenses. How flexible IDRs contribute to T3Es’ function in subverting plant immunity remains unclear. Here, we identify a plant plasma membrane (PM)-associated macromolecular condensation mechanism that governs the sophisticated interplay between T3E XopR and the plant’s Resistance to <em>Pseudomonas syringae pv. maculicola</em> 1 (RPM1)-interacting protein 4 (RIN4) immune complex. Upon deployment into plants, XopR undergoes PM association, percolation clustering, and spanning networking on the PM, ranging from subnanomolar to tens of nanomolar. This spatiotemporal building of the XopR network enables an efficient manipulation of plant surface immune regulators, including a coiled-coil nucleotide-binding leucine-rich repeat receptor (CNL)-guardee complex with highly disordered RIN4. When XopR hijacks and fluidizes the RIN4-RPM1 condensates, <em>Arabidopsis</em> shows reduced RIN4 phosphorylation and diminished RPM1-activated defense <em>in vivo</em>, consistent with XopR-impaired RIN4 phosphorylation by RPM1-interacting protein kinase (RIPK). Our research illuminates the mechanism underlying the dynamic interplay between bacterial T3Es and plant receptor complex condensates during infection.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"183 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695765","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 : 2025-03-24DOI: 10.1016/j.devcel.2025.03.003
Brian K. Wells, Xin Sun
{"title":"Bridging the gap: ICAM1+ cells smooth the transition in the lung","authors":"Brian K. Wells, Xin Sun","doi":"10.1016/j.devcel.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.003","url":null,"abstract":"Transitional cell states are critical in lung injury repair, yet their dynamics in development have not been fully explored. In this issue of <em>Developmental Cell</em>, Ke et al. identify ICAM1+NKX2-1+ progenitors as key transitional cells conserved in the developing human and mouse lung, with plasticity toward generating both airway and alveolar progeny.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"215 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677856","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 : 2025-03-24DOI: 10.1016/j.devcel.2025.02.016
Aicun Li, Zhicheng Gong, Yuhan Long, Yuanpei Li, Chen Liu, Xiao Lu, Qing Li, Xiaoniu He, Hezhe Lu, Kaichun Wu, Yongzhan Nie, Jing Tan, Jing Ye, Han You
{"title":"Lactylation of LSD1 is an acquired epigenetic vulnerability of BRAFi/MEKi-resistant melanoma","authors":"Aicun Li, Zhicheng Gong, Yuhan Long, Yuanpei Li, Chen Liu, Xiao Lu, Qing Li, Xiaoniu He, Hezhe Lu, Kaichun Wu, Yongzhan Nie, Jing Tan, Jing Ye, Han You","doi":"10.1016/j.devcel.2025.02.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.016","url":null,"abstract":"<em>BRAF</em><sup><em>V600E</em></sup> mutant melanomas treated with BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) almost invariably develop drug resistance, accompanied by restored glucose metabolism. How resumed glycolysis controls acquired resistance remains unknown. Here, we identify that lysine-specific demethylase 1 (LSD1) lactylation, induced by re-accumulated lactate in both human and murine BRAFi/MEKi-resistant melanoma cells, selectively drives survival via epigenetic reprogramming. Mechanistically, lactylation of LSD1 promotes its interaction with Fos-related antigen 1 (FosL1), preventing its degradation by E3 ligase tripartite-motif-containing protein 21 (TRIM21) and selectively enhancing its genomic enrichment. We further demonstrate that lactylated LSD1 co-directs gene transcription with FosL1 to repress ferroptosis via interfering with transferrin receptor protein 1 (TFRC)-mediated iron uptake. LSD1 inhibition activates ferroptosis, resulting in drastic regression of drug-resistant murine melanoma when combined with immunotherapy. Our results highlight a crucial role of metabolic rewiring-induced epigenetic reprogramming as a bypass resistance mechanism in BRAFi/MEKi-resistant melanoma, providing a therapeutically actionable strategy to overcome resistance to targeted therapy and immunotherapy.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"183 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677854","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 : 2025-03-24DOI: 10.1016/j.devcel.2025.02.014
Landon L. Moore, Courtney W. Houchen
{"title":"Evolving insights into pancreatic tumor initiation and progression through DCLK1-expressing tuft cells","authors":"Landon L. Moore, Courtney W. Houchen","doi":"10.1016/j.devcel.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.014","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Salas-Escabillas et al. find that tuft cells undergo a tuft-to-neuroendocrine transition, switching from tumor suppressors to tumor promoters via c-Myc in pancreatic ductal adenocarcinoma (PDAC). This result offers exciting insights into PDAC’s aggressiveness, therapy resistance, and high mortality.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"35 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677627","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 : 2025-03-24DOI: 10.1016/j.devcel.2025.02.015
V. Pragathi Masamsetti, Nazmus Salehin, Hani Jieun Kim, Nicole Santucci, Megan Weatherstone, Riley McMahon, Lee L. Marshall, Hilary Knowles, Jane Sun, Josh B. Studdert, Nader Aryamanesh, Ran Wang, Naihe Jing, Pengyi Yang, Pierre Osteil, Patrick P.L. Tam
{"title":"Lineage contribution of the mesendoderm progenitors in the gastrulating mouse embryo","authors":"V. Pragathi Masamsetti, Nazmus Salehin, Hani Jieun Kim, Nicole Santucci, Megan Weatherstone, Riley McMahon, Lee L. Marshall, Hilary Knowles, Jane Sun, Josh B. Studdert, Nader Aryamanesh, Ran Wang, Naihe Jing, Pengyi Yang, Pierre Osteil, Patrick P.L. Tam","doi":"10.1016/j.devcel.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.015","url":null,"abstract":"A population of putative mesendoderm progenitors that can contribute cellular descendants to both mesoderm and endoderm lineages is identified in the gastrulating mouse embryo. These progenitor cells are localized to the posterior epiblast, primitive streak, and nascent mesoderm of mid-streak- (E7.0) to late-streak-stage (E7.5) embryos. Lineage tracing <em>in vivo</em> identified that putative mesendoderm progenitors contribute descendants to the definitive endoderm and the axial mesendoderm of E7.75 embryos and to the endoderm of the foregut and hindgut of the E8.5–8.75 embryos. Differentiation of mouse epiblast stem cells identified that the choice between endoderm and mesoderm cell fates depends on the timing of <em>Mixl1</em> activation upon exit from pluripotency. The knowledge gained on the spatiotemporal distribution of mesendoderm progenitors and the molecular drivers underpinning the divergence of cell lineages in these progenitors enriches our mechanistic understanding of the allocation of the tissue progenitors to germ layer derivatives in early development.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"112 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677855","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 : 2025-03-17DOI: 10.1016/j.devcel.2025.02.013
Luca Braccioli, Teun van den Brand, Noemi Alonso Saiz, Charis Fountas, Patrick H.N. Celie, Justina Kazokaitė-Adomaitienė, Elzo de Wit
{"title":"Identifying cross-lineage dependencies of cell-type-specific regulators in mouse gastruloids","authors":"Luca Braccioli, Teun van den Brand, Noemi Alonso Saiz, Charis Fountas, Patrick H.N. Celie, Justina Kazokaitė-Adomaitienė, Elzo de Wit","doi":"10.1016/j.devcel.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.013","url":null,"abstract":"Correct gene expression levels are crucial for normal development. Advances in genomics enable the inference of gene regulatory programs active during development but cannot capture the complex multicellular interactions occurring during mammalian embryogenesis <em>in utero</em>. <em>In vitro</em> models of mammalian development, like gastruloids, can overcome this limitation. Using time-resolved single-cell chromatin accessibility analysis, we delineated the regulatory profile during mouse gastruloid development, identifying critical drivers of developmental transitions. Gastruloids develop from bipotent progenitor cells driven by the transcription factors (TFs) OCT4, SOX2, and TBXT, differentiating into the mesoderm (characterized by the mesogenin 1 [MSGN1]) and spinal cord (characterized by CDX2). ΔCDX gastruloids fail to form spinal cord, while <em>Msgn1</em> ablation inhibits paraxial mesoderm and spinal cord development. Chimeric gastruloids with ΔMSGN1 and wild-type cells formed both tissues, indicating that inter-tissue communication is necessary for spinal cord formation. Our work has important implications for studying inter-tissue communication and gene regulatory programs in development.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"20 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635584","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 : 2025-03-13DOI: 10.1016/j.devcel.2025.02.012
Deyu Zhang, Songze Song, Jing Lin, Tianxing Ye, Xiao Yang, Qiwei Jiang, Yue Mi, Mengting Zhang, Xiangwei Ge, Yanjie Shen, Peizhe Du, Yanzhu Shi, Xiujuan Zhang, Ling Li, Yanan Zhang, Lihua Ding, Jie Liu, Youzhi Zhang, Shan Gao, Qinong Ye
{"title":"Glutamine binds HSC70 to transduce signals inhibiting IFN-β-mediated immunogenic cell death","authors":"Deyu Zhang, Songze Song, Jing Lin, Tianxing Ye, Xiao Yang, Qiwei Jiang, Yue Mi, Mengting Zhang, Xiangwei Ge, Yanjie Shen, Peizhe Du, Yanzhu Shi, Xiujuan Zhang, Ling Li, Yanan Zhang, Lihua Ding, Jie Liu, Youzhi Zhang, Shan Gao, Qinong Ye","doi":"10.1016/j.devcel.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.012","url":null,"abstract":"Glutamine plays a role in cell signaling that regulates gene expression and impacts tumorigenesis. However, it is still unclear how glutamine transduces signals in cells. Here, we show that glutamine binds to heat shock cognate protein 70 (HSC70) to stimulate the deubiquitinase otubain domain containing protein (OTUD4) independently of known glutamine metabolic or signaling pathways, resulting in lactate dehydrogenase A (LDHA) stabilization via the microautophagy-lysosome pathway, increased lactate production and decreased expression of interferon (IFN)-β and its targets, hallmarks of immunogenic cell death (ICD). In cancer cell lines and patient-derived organoids and xenografts, glutamine depletion or glutamine transport inhibition combined with ICD-inducing chemotherapeutic drugs synergistically activates IFN-β, promotes CD8<sup>+</sup> T cell recruitment, and inhibits cancer cell growth via the OTUD4/LDHA axis. CD8 expression is negatively correlated with expression of the glutamine transporter alanine/serine/cysteine transporter 2 (ASCT2), OTUD4, and LDHA in cancer patients. Thus, we identify an intracellular glutamine signaling pathway, and targeting this pathway is a promising strategy for cancer treatment.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"87 2 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608696","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 : 2025-03-12DOI: 10.1016/j.devcel.2025.02.011
Aubrie M. Stricker, M. Shane Hutson, Andrea Page-McCaw
{"title":"Piezo-dependent surveillance of matrix stiffness generates transient cells that repair the basement membrane","authors":"Aubrie M. Stricker, M. Shane Hutson, Andrea Page-McCaw","doi":"10.1016/j.devcel.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.011","url":null,"abstract":"Basement membranes are extracellular matrix sheets separating tissue layers and providing mechanical support, and collagen IV (Col4) is their most abundant structural protein. Although basement membranes are repaired after damage, little is known about repair, including whether and how damage is detected, what cells repair the damage, and how repair is controlled to avoid fibrosis. Using the intestinal basement membrane of adult <em>Drosophila</em> as a model, we show that after basement membrane damage, there is a sharp increase in enteroblasts transiently expressing Col4, termed “matrix mender” cells. Enteroblast-derived Col4 is specifically required for matrix repair. The increase in matrix mender cells requires the mechanosensitive ion channel Piezo, expressed in intestinal stem cells. Matrix menders are induced by the loss of matrix stiffness, as specifically inhibiting Col4 crosslinking is sufficient for Piezo-dependent induction of matrix mender cells. Our data suggest that epithelial stem cells control basement membrane integrity by monitoring stiffness.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"3 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599382","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 : 2025-03-10DOI: 10.1016/j.devcel.2025.02.009
Dhananjay Huilgol, Jesse M. Levine, William Galbavy, Bor-Shuen Wang, Z. Josh Huang
{"title":"Orderly specification and precise laminar deployment of mouse cortical projection neuron types through intermediate progenitors","authors":"Dhananjay Huilgol, Jesse M. Levine, William Galbavy, Bor-Shuen Wang, Z. Josh Huang","doi":"10.1016/j.devcel.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.009","url":null,"abstract":"The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis (dNG) or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the “inside-out” model, whereby successive generations of PNs sequentially migrate first to deep and then progressively to more superficial layers. However, its biological significance remains unclear, and the role of iNG in this process is unknown. Using genetic strategies linking PN birth dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviates from a stringent inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"19 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582492","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}