Developmental cellPub Date : 2025-05-05DOI: 10.1016/j.devcel.2025.04.007
Mehmet-Yunus Comar, Bernardo Oldak, Jacob H. Hanna
{"title":"Human-specific contributors to cleavage-stage embryonic arrest during maternal to zygotic transition","authors":"Mehmet-Yunus Comar, Bernardo Oldak, Jacob H. Hanna","doi":"10.1016/j.devcel.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.007","url":null,"abstract":"Understanding the functional regulatory landscape of maternal-to-zygotic transition (MZT) during early human embryo development remains a challenge. In this issue of <em>Developmental Cell</em>, Guo et al. assessed single-cell allele-specific transcriptomics from human preimplantation embryos and identified DPRX and ARGFX genes as pivotal factors whose hampered activation underlies cleavage-stage embryonic arrest.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"60 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905433","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 : 2025-05-05DOI: 10.1016/j.devcel.2025.04.009
Shuyan Wang, Nianping Liu, Kun Qu
{"title":"What insights can spatiotemporal esophageal atlases and deep learning bring to engineering the esophageal mucosa?","authors":"Shuyan Wang, Nianping Liu, Kun Qu","doi":"10.1016/j.devcel.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.009","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Yang et al. present an integrated experimental and computational platform that maps the spatiotemporal development of the human esophagus and predicts key signaling pathways governing epithelial differentiation. Their findings enable a xeno-free, scalable strategy for generating esophageal mucosa from human pluripotent stem cells (hPSCs), demonstrating the power of combining spatial developmental data with deep learning.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"46 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905434","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 : 2025-05-05DOI: 10.1016/j.devcel.2025.04.003
Maria Azkanaz, Dimitrios Laskaris, Jacco van Rheenen
{"title":"Stemness in flux: Dissecting intestinal crypt organization with multimodal approaches","authors":"Maria Azkanaz, Dimitrios Laskaris, Jacco van Rheenen","doi":"10.1016/j.devcel.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.003","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Banjac et al. integrate lineage tracing, single-cell RNA sequencing, and mathematical modeling to reveal that stem cells at the crypt base drive the decision between secretory and absorptive lineage commitment. Their findings highlight the central role of crypt-bottom Lgr5<sup>+</sup> cells in maintaining intestinal epithelium homeostasis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"9 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905579","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 : 2025-05-02DOI: 10.1016/j.devcel.2025.04.008
Blessy Paul, Holly Merta, Rupali Ugrankar-Banerjee, Monica R. Hensley, Son Tran, Goncalo Dias do Vale, Lauren Zacherias, Charles K. Hewett, Jeffrey G. McDonald, Joan Font-Burgada, Thomas P. Mathews, Steven A. Farber, W. Mike Henne
{"title":"Paraoxonase-like APMAP maintains endoplasmic-reticulum-associated lipid and lipoprotein homeostasis","authors":"Blessy Paul, Holly Merta, Rupali Ugrankar-Banerjee, Monica R. Hensley, Son Tran, Goncalo Dias do Vale, Lauren Zacherias, Charles K. Hewett, Jeffrey G. McDonald, Joan Font-Burgada, Thomas P. Mathews, Steven A. Farber, W. Mike Henne","doi":"10.1016/j.devcel.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.008","url":null,"abstract":"Oxidative stress perturbs lipid homeostasis and contributes to metabolic diseases. Though ignored when compared with mitochondrial oxidation, the endoplasmic reticulum (ER) generates reactive oxygen species requiring antioxidant quality control. Using multi-organismal profiling featuring <em>Drosophila</em>, zebrafish, and mammalian hepatocytes, here we characterize the paraoxonase-like C20orf3/adipocyte plasma-membrane-associated protein (APMAP) as an ER-localized antioxidant that suppresses ER lipid oxidation to safeguard ER function. APMAP-depleted cells exhibit defective ER morphology, ER stress, and lipid peroxidation dependent on ER-oxidoreductase 1α (ERO1A), as well as sensitivity to ferroptosis and defects in ApoB-lipoprotein homeostasis. Similarly, organismal APMAP depletion in <em>Drosophila</em> and zebrafish perturbs ApoB-lipoprotein homeostasis. Strikingly, APMAP loss is rescued with chemical antioxidant N-acetyl-cysteine (NAC). Lipidomics identifies that APMAP loss elevates phospholipid peroxidation and boosts ceramides—signatures of lipid stress. Collectively, we propose that APMAP is an ER-localized antioxidant that promotes lipid and lipoprotein homeostasis in the ER network.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897892","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 : 2025-05-01DOI: 10.1016/j.devcel.2025.04.005
Zhijie Li, Kelsey E. Koch, Dakota T. Thompson, Dana M. Van der Heide, Jeremy Chang, Christopher M. Franke, Mohammed O. Suraju, Anna C. Beck, Allison W. Lorenzen, Jeffrey R. White, Nicholas I. Bartschat, Mikhail V. Kulak, David K. Meyerholz, Colin Kenny, Ronald J. Weigel
{"title":"Sumoylated Etv1 establishes mouse mammary cancer stem cells that support tumorigenesis by non-stem cancer cells","authors":"Zhijie Li, Kelsey E. Koch, Dakota T. Thompson, Dana M. Van der Heide, Jeremy Chang, Christopher M. Franke, Mohammed O. Suraju, Anna C. Beck, Allison W. Lorenzen, Jeffrey R. White, Nicholas I. Bartschat, Mikhail V. Kulak, David K. Meyerholz, Colin Kenny, Ronald J. Weigel","doi":"10.1016/j.devcel.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.005","url":null,"abstract":"The small ubiquitin-like modifier (SUMO) pathway is required for maintenance of cancer stem cells/tumor-initiating cells (CSCs/TICs), which drive tumorigenesis when transplanted into immunocompromised mice. We found that inhibition of the SUMO pathway blocked Neu-mediated mammary oncogenesis and inhibited the function of CSCs/TICs without effects on normal mammary stem cells. Transcriptomic analysis implicated SUMO-conjugated Etv1 as being critical for oncogenesis. After SUMO pathway inhibition, a SUMO-mimetic Etv1 protein, created by a fusion with SUMO1 or SUMO2, established a stem-like cell capable of tumorigenesis, whereas a SUMO-resistant Etv1 protein established a proliferative, non-tumorigenic cell. In mixing experiments, stem-like cells induced tumorigenesis by non-stem cells. We conclude that SUMO-conjugated Etv1 is necessary to maintain the CSC/TIC phenotype and that crosstalk between stem and non-stem cells is crucial for tumorigenesis. The findings demonstrate dynamic interactions between heterogeneous cell types to drive tumorigenesis, which has implications for future cancer therapeutic development.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"11 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893219","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 : 2025-04-29DOI: 10.1016/j.devcel.2025.04.006
Ting-Ting Yuan, Yu-Rui Feng, Hua Cheng, Shuiyuan Cheng, Ying-Tang Lu
{"title":"Bacteria suppress immune responses in Arabidopsis by inducing methylglyoxal accumulation and promoting H2O2 scavenging","authors":"Ting-Ting Yuan, Yu-Rui Feng, Hua Cheng, Shuiyuan Cheng, Ying-Tang Lu","doi":"10.1016/j.devcel.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.006","url":null,"abstract":"Various reactive small molecules, naturally produced via cellular metabolism, function in plant immunity. However, how pathogens use plant metabolites to promote their infection is poorly understood. Here, we identified that infection with a virulent bacterial strain represses glyoxalase I (GLYI) activity, leading to elevated levels of methylglyoxal (MG) in <em>Arabidopsis</em>. Genetic analysis of GLYIs further supports that MG promotes bacterial infection. Mechanistically, MG modifies TRIPHOSPHATE TUNNEL METALLOENZYME2 (TTM2) at Arg-351, facilitating its interaction with CATALASE2 (CAT2), resulting in higher CAT2 activity and lower hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) accumulation. Taken together, we demonstrate that the bacterial pathogen harnesses the plant metabolite MG to promote its infection by scavenging H<sub>2</sub>O<sub>2</sub>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"43 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885265","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 : 2025-04-24DOI: 10.1016/j.devcel.2025.04.004
Wanxin Guo, Congcong Zhang, Qianjun Zhou, Tianxiang Chen, Xin Xu, Jianfeng Zhang, Xuewen Yu, Han Wu, Xiao Zhang, Lifang Ma, Kun Qian, Daniel J. Klionsky, Rui Kang, Guido Kroemer, Yongchun Yu, Daolin Tang, Jiayi Wang
{"title":"Mitochondrial CCN1 drives ferroptosis via fatty acid β-oxidation","authors":"Wanxin Guo, Congcong Zhang, Qianjun Zhou, Tianxiang Chen, Xin Xu, Jianfeng Zhang, Xuewen Yu, Han Wu, Xiao Zhang, Lifang Ma, Kun Qian, Daniel J. Klionsky, Rui Kang, Guido Kroemer, Yongchun Yu, Daolin Tang, Jiayi Wang","doi":"10.1016/j.devcel.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.004","url":null,"abstract":"Ferroptosis is a type of oxidative cell death, although its key metabolic processes remain incompletely understood. Here, we employ a comprehensive multiomics screening approach that identified cellular communication network factor 1 (CCN1) as a metabolic catalyst of ferroptosis. Upon ferroptosis induction, CCN1 relocates to mitochondrial complexes, facilitating electron transfer flavoprotein subunit alpha (ETFA)-dependent fatty acid β-oxidation. Compared with a traditional carnitine O-palmitoyltransferase 2 (CPT2)-ETFA pathway, the CCN1-ETFA pathway provides additional substrates for mitochondrial reactive oxygen species production, thereby stimulating ferroptosis through lipid peroxidation. A high-fat diet can enhance the anticancer efficacy of ferroptosis in lung cancer mouse models, depending on CCN1. Furthermore, primary lung cancer cells derived from patients with hypertriglyceridemia or high CCN1 expression demonstrate increased susceptibility to ferroptosis <em>in vitro</em> and <em>in vivo</em>. These findings do not only identify the metabolic role of mitochondrial CCN1 but also establish a strategy for enhancing ferroptosis-based anticancer therapies.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"219 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866994","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 : 2025-04-22DOI: 10.1016/j.devcel.2025.04.002
Kehui Zhu, Jinchao Chen, Long Zhao, Fangfang Lu, Jia Deng, Xuelei Lin, Chongsheng He, Doris Wagner, Jun Xiao
{"title":"Dynamic control of H2A.Zub and H3K27me3 by ambient temperature during cell fate determination in Arabidopsis","authors":"Kehui Zhu, Jinchao Chen, Long Zhao, Fangfang Lu, Jia Deng, Xuelei Lin, Chongsheng He, Doris Wagner, Jun Xiao","doi":"10.1016/j.devcel.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.002","url":null,"abstract":"Crucial to plant development, ambient temperature triggers intricate mechanisms enabling adaptive responses to temperature variations. The precise coordination of chromatin modifications in shaping cell developmental fate under diverse temperatures remains elusive. Our study, integrating comprehensive transcriptome, epigenome profiling, and genetics, demonstrates that lower ambient temperature (16°C) partially restores developmental defects caused by H3K27me3 loss in <em>prc2</em> mutants by specifically depositing H2A.Zub at ectopically expressed embryonic genes in <em>Arabidopsis</em>, such as <em>ABA INSENSITIVE 3</em> (<em>ABI3</em>) and <em>LEAFY COTYLEDON 1</em> (<em>LEC1</em>). This deposition leads to downregulation of these genes and compensates for H3K27me3 depletion. Polycomb-repressive complex 1 (PRC1)-catalyzed H2A.Zub and PRC2-catalyzed H3K27me3 play roles in silencing transcription of embryonic genes for post-germination development. Low-temperature-induced reduction of TOE1 protein level decelerates H2A.Z turnover at specific loci, sustaining repression of embryonic genes and alleviating requirement for PRC2-H3K27me3 at post-germination stage. Our findings offer mechanistic insights into the cooperative epigenetic layers, facilitating plant adaptation to varying environmental temperatures.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"29 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857780","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.04.001
Danfeng Wang, Hongyan Guo, Xinru Gong, Lichao Chen, Huifang Lin, Shiping Wang, Tianpeng Feng, Yanyan Yi, Wan Wang, Shuhua Yang, Jie Le, Lixin Zhang, Jianru Zuo
{"title":"Nitric oxide controls stomatal development and stress responses by inhibiting MPK6 phosphorylation via S-nitrosylation in Arabidopsis","authors":"Danfeng Wang, Hongyan Guo, Xinru Gong, Lichao Chen, Huifang Lin, Shiping Wang, Tianpeng Feng, Yanyan Yi, Wan Wang, Shuhua Yang, Jie Le, Lixin Zhang, Jianru Zuo","doi":"10.1016/j.devcel.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.001","url":null,"abstract":"In plants, stomata on the aerial epidermis play critical roles in various biological processes, including gas exchange, photosynthesis, transpiration, and immunity. Stomatal development is negatively and positively controlled by the mitogen-activated protein kinase (MAPK) cascade and nitric oxide (NO), respectively. However, the regulatory scheme of stomatal development by these signaling pathways remains elusive. Here, we show that NO-controlled stomatal development in <em>Arabidopsis</em> is genetically dependent on <em>MPK3</em> and <em>MPK6</em>. Moreover, NO-controlled <em>S</em>-nitrosylation of MPK6 at cysteine (Cys)-201 inhibits its phosphorylation, resulting in the stabilization of SPEECHLESS (SPCH), a master regulator of stomatal lineage initiation, thereby promoting stomatal development. An <em>MPK6</em><sup><em>C201S</em></sup> mutation confers NO insensitivity during stomatal development and stress responses. We propose that NO positively controls stomatal development and stress responses by inhibiting the MPK6 activity via <em>S</em>-nitrosylation, thus identifying a mechanism linking the coupled NO-MAPK signaling to specific biological outputs.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"56 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853191","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.014
Nicholas R. Smith, Nicole R. Giske, Sidharth K. Sengupta, Patrick Conley, John R. Swain, Ashvin Nair, Kathryn L. Fowler, Christopher Klocke, Yeon Jung Yoo, Ashley N. Anderson, Nasim Sanati, Kristof Torkenczy, Andrew C. Adey, Jared M. Fischer, Guanming Wu, Melissa H. Wong
{"title":"Dual states of murine Bmi1-expressing intestinal stem cells drive epithelial development utilizing non-canonical Wnt signaling","authors":"Nicholas R. Smith, Nicole R. Giske, Sidharth K. Sengupta, Patrick Conley, John R. Swain, Ashvin Nair, Kathryn L. Fowler, Christopher Klocke, Yeon Jung Yoo, Ashley N. Anderson, Nasim Sanati, Kristof Torkenczy, Andrew C. Adey, Jared M. Fischer, Guanming Wu, Melissa H. Wong","doi":"10.1016/j.devcel.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.014","url":null,"abstract":"Intestinal epithelial development and homeostasis critically rely upon balanced stem cell proliferation, involving slow-cycling/label-retaining and active-cycling/canonical Wnt-dependent intestinal stem cell (ISC) subtypes. ISC regulation during development remains poorly understood but has important implications for establishing key mechanisms governing tissue maintenance. Herein, we identify Bmi1<sup>+</sup> cells as functional stem cells present in early murine intestinal development, prior to Lgr5-expressing ISCs. Lineage tracing and single-cell RNA sequencing identify that Bmi1<sup>+</sup> ISCs can trace to Lgr5<sup>+</sup> ISCs and other differentiated lineages. Initially highly proliferative, Bmi1<sup>+</sup> ISCs transition to slow-cycling states as Lgr5<sup>+</sup> ISCs emerge. Non-canonical Wnt signaling regulates the proliferative Bmi1<sup>+</sup> cell state. These findings highlight the dynamic interplay between stem cell populations and the opposing Wnt pathways that govern proliferation—ultimately having implications for tissue development, homeostasis, regeneration, and tumorigenesis. Understanding these fundamental developmental mechanisms is critical for understanding adult intestinal maintenance.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"10 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853192","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}