Developmental cell最新文献_第5页

mTor limits autophagy to facilitate cell volume expansion and rapid wound repair in Drosophila embryos 在果蝇胚胎中，mTor限制自噬以促进细胞体积扩张和快速伤口修复

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-16 DOI: 10.1016/j.devcel.2024.12.039

Gordana Scepanovic, Negar Balaghi, Katheryn E. Rothenberg, Rodrigo Fernandez-Gonzalez

{"title":"mTor limits autophagy to facilitate cell volume expansion and rapid wound repair in Drosophila embryos","authors":"Gordana Scepanovic, Negar Balaghi, Katheryn E. Rothenberg, Rodrigo Fernandez-Gonzalez","doi":"10.1016/j.devcel.2024.12.039","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.039","url":null,"abstract":"Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the increase in the volume of the cells adjacent to the wound. The mechanistic target of rapamycin (mTor) complex 1 (TORC1) is associated with cell growth. We found that disrupting TORC1 signaling in Drosophila embryos prevented cell volume increases and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Five-dimensional microscopy demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. mTor inhibition increased autophagy, and activating autophagy prevented cell volume expansion and slowed down wound closure. Finally, reducing autophagy in embryos with disrupted TORC1 signaling rescued cell volume changes and rapid wound repair. Together, our results show that TORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"38 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987025","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}

引用次数: 0

The regulatory landscape of 5′ UTRs in translational control during zebrafish embryogenesis 斑马鱼胚胎发生过程中5 ' utr在翻译控制中的调控前景

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-15 DOI: 10.1016/j.devcel.2024.12.038

Madalena M. Reimão-Pinto, Sebastian M. Castillo-Hair, Georg Seelig, Alexander F. Schier

{"title":"The regulatory landscape of 5′ UTRs in translational control during zebrafish embryogenesis","authors":"Madalena M. Reimão-Pinto, Sebastian M. Castillo-Hair, Georg Seelig, Alexander F. Schier","doi":"10.1016/j.devcel.2024.12.038","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.038","url":null,"abstract":"The 5′ UTRs of mRNAs are critical for translation regulation during development, but their in vivo regulatory features are poorly characterized. Here, we report the regulatory landscape of 5′ UTRs during early zebrafish embryogenesis using a massively parallel reporter assay of 18,154 sequences coupled to polysome profiling. We found that the 5′ UTR suffices to confer temporal dynamics to translation initiation and identified 86 motifs enriched in 5′ UTRs with distinct ribosome recruitment capabilities. A quantitative deep learning model, Danio Optimus 5-Prime (DaniO5P), identified a combined role for 5′ UTR length, translation initiation site context, upstream AUGs, and sequence motifs on ribosome recruitment. DaniO5P predicts the activities of maternal and zygotic 5′ UTR isoforms and indicates that modulating 5′ UTR length and motif grammar contributes to translation initiation dynamics. This study provides a first quantitative model of 5′ UTR-based translation regulation in development and lays the foundation for identifying the underlying molecular effectors.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"49 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981360","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}

引用次数: 0

Calcium-dependent protein kinases CPK3/4/6/11 and 27 respond to osmotic stress and activate SnRK2s in Arabidopsis 钙依赖性蛋白激酶 CPK3/4/6/11 和 27 对拟南芥的渗透胁迫做出反应并激活 SnRK2s

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-14 DOI: 10.1016/j.devcel.2024.12.036

Qingzhong Li, Tao Hu, Tianjiao Lu, Bo Yu, Yang Zhao

{"title":"Calcium-dependent protein kinases CPK3/4/6/11 and 27 respond to osmotic stress and activate SnRK2s in Arabidopsis","authors":"Qingzhong Li, Tao Hu, Tianjiao Lu, Bo Yu, Yang Zhao","doi":"10.1016/j.devcel.2024.12.036","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.036","url":null,"abstract":"Drought and salinity are significant environmental threats that cause hyperosmotic stress in plants, which respond with a transient elevation of cytosolic Ca2+ and activation of Snf1-related protein kinase 2s (SnRK2s) and downstream responses. The exact regulators decoding Ca2+ signals to activate downstream responses remained unclear. Here, we show that the calcium-dependent protein kinases CPK3/4/6/11 and 27 respond to moderate osmotic stress and dehydration to activate SnRK2 phosphorylation in Arabidopsis. Using quantitative phosphoproteomics in a higher-order mutant lacking 12 pyrabactin resistance 1-like (PYL) abscisic acid (ABA) receptors, we identified six CPKs that are phosphorylated under osmotic stress. CPK3/4/6/11/27 phosphorylate the SnRK2s on multiple phosphosites within the activation loop. The cpk3/4/6/11/27 mutant is defective in SnRK2 activation, seed germination, and seedling growth under mild osmotic stress. Our findings elucidate the critical roles of CPK3/4/6/11/27 in decoding Ca2+ signals to activate SnRK2s and demonstrate a CPK-SnRK2 kinase cascade controlling osmotic stress responses in plants.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"51 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974564","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}

引用次数: 0

The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms 小鼠胎盘血管的空间分区由表观遗传机制决定

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-14 DOI: 10.1016/j.devcel.2024.12.037

Stephanie Gehrs, Moritz Jakab, Ewgenija Gutjahr, Zuguang Gu, Dieter Weichenhan, Jan-Philipp Mallm, Carolin Mogler, Matthias Schlesner, Christoph Plass, Katharina Schlereth, Hellmut G. Augustin

{"title":"The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms","authors":"Stephanie Gehrs, Moritz Jakab, Ewgenija Gutjahr, Zuguang Gu, Dieter Weichenhan, Jan-Philipp Mallm, Carolin Mogler, Matthias Schlesner, Christoph Plass, Katharina Schlereth, Hellmut G. Augustin","doi":"10.1016/j.devcel.2024.12.037","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.037","url":null,"abstract":"The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"22 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974567","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}

引用次数: 0

Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest 等位基因转录组学分析鉴定了prd样同源盒基因在人类胚胎裂解期阻滞中的作用

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-13 DOI: 10.1016/j.devcel.2024.12.031

Qianying Guo, Fanqing Xu, Shi Song, Siming Kong, Fan Zhai, Yuwen Xiu, Dandan Liu, Ming Li, Ying Lian, Ling Ding, Qian Liu, Ming Yang, Zhengrong Du, Nan Wang, Chuan Long, Xiaomeng Wang, Yuqian Wang, Zhiqiang Yan, Jie Qiao, Liying Yan, Peng Yuan

{"title":"Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest","authors":"Qianying Guo, Fanqing Xu, Shi Song, Siming Kong, Fan Zhai, Yuwen Xiu, Dandan Liu, Ming Li, Ying Lian, Ling Ding, Qian Liu, Ming Yang, Zhengrong Du, Nan Wang, Chuan Long, Xiaomeng Wang, Yuqian Wang, Zhiqiang Yan, Jie Qiao, Liying Yan, Peng Yuan","doi":"10.1016/j.devcel.2024.12.031","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.031","url":null,"abstract":"Cleavage-stage arrest in human embryos substantially limits the success rate of infertility treatment, with maternal-to-zygotic transition (MZT) abnormalities being a potential contributor. However, the underlying mechanisms and regulators remain unclear. Here, by performing allelic transcriptome analysis on human preimplantation embryos, we accurately quantified MZT progression by allelic ratio and identified a fraction of 8-cell embryos, at the appropriate developmental time point and exhibiting normal morphology, were in transcriptionally arrested status. Furthermore, we identified PAIRED (PRD)-like homeobox transcription factors divergent paired-related homeobox (DPRX) and arginine-fifty homeobox (ARGFX) as factors involved in MZT, whose deficiency severely impairs MZT and lineage specification and leads to aberrant retention of histone acetylation. By reversing the acetylation retention caused by DPRX and ARGFX defects, embryonic arrest can be partially rescued. Our study identifies factors involved in human MZT and elucidates the etiology underlying human cleavage-stage arrest.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"21 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967969","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}

引用次数: 0

Cellular damage triggers mechano-chemical control of cell wall dynamics and patterned cell divisions in plant healing 在植物愈合过程中，细胞损伤触发细胞壁动力学和细胞分裂的机械化学控制

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-13 DOI: 10.1016/j.devcel.2024.12.032

Luciano Martín Di Fino, Muhammad Shahzad Anjam, Maarten Besten, Andriani Mentzelopoulou, Vassilis Papadakis, Nageena Zahid, Luis Alonso Baez, Nicola Trozzi, Mateusz Majda, Xuemin Ma, Thorsten Hamann, Joris Sprakel, Panagiotis N. Moschou, Richard S. Smith, Peter Marhavý

引用次数: 0

Nanopore RNA direct sequencing identifies that m6A modification is essential for sorbitol-controlled resistance to Alternaria alternata in apple 纳米孔RNA直接测序识别m6A修改对sorbitol-controlled至关重要阻力主产苹果

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-13 DOI: 10.1016/j.devcel.2024.12.033

Zhihua Song, Qing Yang, Biying Dong, Shengjie Wang, Jingyi Xue, Ni Liu, Xiaomiao Zhou, Na Li, Abhaya M. Dandekar, Lailiang Cheng, Dong Meng, Yujie Fu

{"title":"Nanopore RNA direct sequencing identifies that m6A modification is essential for sorbitol-controlled resistance to Alternaria alternata in apple","authors":"Zhihua Song, Qing Yang, Biying Dong, Shengjie Wang, Jingyi Xue, Ni Liu, Xiaomiao Zhou, Na Li, Abhaya M. Dandekar, Lailiang Cheng, Dong Meng, Yujie Fu","doi":"10.1016/j.devcel.2024.12.033","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.033","url":null,"abstract":"Sorbitol, a main photosynthate and transport carbohydrate in all tree fruit species in Rosaceae, acts as a signal controlling resistance against Alternaria (A.) alternata in apple by altering the expression of the MdNLR16 resistance gene via the MdWRKY79 transcription factor. However, it is not known if N6-methyladenosine (m6A) methylation of the mRNAs of these genes participates in the process. Here, we found that decreased sorbitol synthesis in apple leaves leads to a transcriptome-wide reduction in the m6A modification, with fewer transcripts containing two or more methylation sites. We identified two methyltransferases, MdVIR1 and MdVIR2, that respond to sorbitol and A. alternata inoculation and positively control resistance to A. alternata. MdVIR1 and MdVIR2 act on MdWRKY79 and MdNLR16 mRNAs, and the resulting m6A modification stabilizes their mRNAs and improves translation efficiency. These data identify that m6A modification through MdVIR1 and MdVIR2 methyltransferases is essential for sorbitol-controlled resistance to A. alternata.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"47 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967968","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}

引用次数: 0

Feedback regulation of m6A modification creates local auxin maxima essential for rice microsporogenesis m6A修饰的反馈调控产生了水稻小孢子发生所必需的局部生长素最大值

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-13 DOI: 10.1016/j.devcel.2024.12.034

Peng Cheng, Hu Zhao, Songyao Zhang, Zhanxiang Zong, Chengxiang Li, Luchang Ming, Weibo Xie, Hao Yu

{"title":"Feedback regulation of m6A modification creates local auxin maxima essential for rice microsporogenesis","authors":"Peng Cheng, Hu Zhao, Songyao Zhang, Zhanxiang Zong, Chengxiang Li, Luchang Ming, Weibo Xie, Hao Yu","doi":"10.1016/j.devcel.2024.12.034","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.034","url":null,"abstract":"N6-methyladenosine (m6A) RNA modification and its effectors control various plant developmental processes, yet whether and how these effectors are transcriptionally controlled to confer functional specificity so far remain elusive. Herein, we show that a rice C2H2 zinc-finger protein, OsZAF, specifically activates the expression of OsFIP37 encoding a core component of the m6A methyltransferase complex during microsporogenesis in rice anthers. OsFIP37, in turn, facilitates m6A modification and stabilization of an auxin biosynthesis gene OsYUCCA3 to promote auxin biosynthesis in anthers. This elevates auxin levels coinciding with upregulation of an auxin response factor OsARF12 that positively controls OsZAF, thus creating a positive feedback circuit whereby OsFIP37 is continuously activated for local auxin production. Our findings suggest that OsZAF-dependent feedback regulation of m6A modification is integral to local auxin biosynthesis and signaling in anthers, which facilitates the timely generation of auxin maxima required for male meiosis in rice.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"204 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967967","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}

引用次数: 0

Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a PRC2-dependent mechanism 单细胞RNA-seq鉴定由prc2依赖机制指导的小鼠生殖系X染色体延长再激活动力学

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-10 DOI: 10.1016/j.devcel.2024.12.028

Yaqiong Liu, Xianzhong Lau, Prabhakaran Munusamy, Carlos M. Abascal Sherwell Sanchez, Daniel Snell, Mahesh Sangrithi

{"title":"Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a PRC2-dependent mechanism","authors":"Yaqiong Liu, Xianzhong Lau, Prabhakaran Munusamy, Carlos M. Abascal Sherwell Sanchez, Daniel Snell, Mahesh Sangrithi","doi":"10.1016/j.devcel.2024.12.028","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.028","url":null,"abstract":"Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F1 mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells. Establishment of germ cell sexual dimorphism and X chromosome dosage compensation states in vivo are temporally linked to XCR. Allele-specific analysis evidence that the reactivating X chromosome is minimally active in embryonic day (E)9.5 female PGCs, reactivates gradually, and reaches parity to the active X chromosome in E16.5 oogonia. While Xist is repressed from E10.5 onward, epigenetic memory of X inactivation persists from self-sustained polycomb repressive complex 2 (PRC2) activity. The reactivating X is asymmetrically enriched for histone 3-lysine-27-trimethylation (H3K27me3) at E13.5, which is later reversed, permitting germline gene expression. Our findings relate XCR with PRC2 function in promoting female meiosis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939563","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}

引用次数: 0

DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma DYRK1A-TGF-β信号轴决定肝癌对OXPHOS抑制的敏感性

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-01-10 DOI: 10.1016/j.devcel.2024.12.035

Ying Cao, Ruolan Qian, Ruilian Yao, Quan Zheng, Chen Yang, Xupeng Yang, Shuyi Ji, Linmen Zhang, Shujie Zhan, Yiping Wang, Tianshi Wang, Hui Wang, Chun-Ming Wong, Shengxian Yuan, Christopher Heeschen, Qiang Gao, René Bernards, Wenxin Qin, Cun Wang

{"title":"DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma","authors":"Ying Cao, Ruolan Qian, Ruilian Yao, Quan Zheng, Chen Yang, Xupeng Yang, Shuyi Ji, Linmen Zhang, Shujie Zhan, Yiping Wang, Tianshi Wang, Hui Wang, Chun-Ming Wong, Shengxian Yuan, Christopher Heeschen, Qiang Gao, René Bernards, Wenxin Qin, Cun Wang","doi":"10.1016/j.devcel.2024.12.035","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.035","url":null,"abstract":"Intervening in mitochondrial oxidative phosphorylation (OXPHOS) has emerged as a potential therapeutic strategy for certain types of cancers. Employing kinome-based CRISPR screen, we find that knockout of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) synergizes with OXPHOS inhibitor IACS-010759 in liver cancer cells. Targeting DYRK1A combined with OXPHOS inhibitors activates TGF-β signaling, which is crucial for OXPHOS-inhibition-triggered cell death. Mechanistically, upregulation of glutamine transporter solute carrier family 1 member 5 (SLC1A5) transcription compensates for the increased glutamine requirement upon OXPHOS inhibition. DYRK1A directly phosphorylates SMAD3 Thr132, thereby suppressing the negative impact of TGF-β signaling on transcription of SLC1A5, leading to intrinsic resistance of liver cancer cells to OXPHOS inhibition. Moreover, we demonstrate the therapeutic efficacy of IACS-010759 in combination with DYRK1A inhibition in multiple liver cancer models, including xenografts, patient-derived xenografts, and spontaneous tumor model. Our study elucidates how the DYRK1A-TGF-β signaling axis controls the response of tumor cells to OXPHOS inhibition and provides valuable insights into targeting OXPHOS for liver cancer therapy.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939568","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}

引用次数: 0