Developmental cell最新文献_第6页

Ben-Zion Shilo (1951-2025). 本-锡安·希洛（1951-2025）。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-08-18 DOI: 10.1016/j.devcel.2025.07.013

Stanislav Y Shvartsman

引用次数: 0

ER-phagy and proteostasis defects prime pancreatic epithelial state changes in KRAS-mediated oncogenesis 在kras介导的肿瘤发生中，er吞噬和蛋白酶抑制缺陷导致胰腺上皮状态的改变

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-14 DOI: 10.1016/j.devcel.2025.07.016

Carla Salomó Coll, Marisa Di Monaco, Jocelyn Holkham, Matthew Smith, Morwenna Muir, Philippe Gautier, Hywel Dunn-Davies, Xiaozhong Zheng, Roopesh Krishnankutty, Alain J. Kemp, Katie Winnington-Ingram, Alex von Kriegsheim, Jennifer P. Morton, Natalia Jimenez-Moreno, Damian Mole, Simon Wilkinson

{"title":"ER-phagy and proteostasis defects prime pancreatic epithelial state changes in KRAS-mediated oncogenesis","authors":"Carla Salomó Coll, Marisa Di Monaco, Jocelyn Holkham, Matthew Smith, Morwenna Muir, Philippe Gautier, Hywel Dunn-Davies, Xiaozhong Zheng, Roopesh Krishnankutty, Alain J. Kemp, Katie Winnington-Ingram, Alex von Kriegsheim, Jennifer P. Morton, Natalia Jimenez-Moreno, Damian Mole, Simon Wilkinson","doi":"10.1016/j.devcel.2025.07.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.016","url":null,"abstract":"Pre-malignant transformation of pancreatic acinar cells by oncogenic Kras is dependent upon stochastic emergence of metaplastic cell states. Here, we reveal that an early, transcriptionally mediated effect of Kras is sporadic failure of proteostatic endoplasmic reticulum (ER)-phagy. Genetically altered mice deficient in ER-phagy demonstrate that this event cooperates with Kras to drive acinar-ductal metaplasia (ADM) and subsequent cancer. Mechanistically, proteomics and high-resolution imaging uncover pathologic aggregation of a subset of ER proteins, including the injury marker REG3B, resulting from failure to physically interact with the ER-phagy receptor CCPG1. Spatial transcriptomics demonstrate that the appearance of sporadic intracellular aggregates upon Kras activation marks rare acinar cells existing in an injured, ADM-primed state. Importantly, engineered mutants of REG3B establish that aggregate formation is sufficient to directly engender this epithelial cell state. Pancreatic cancer can thus arise from stochastic pathologic protein aggregates that are influenced by, and cooperate with, an oncogene.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"5 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851399","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

On-demand delivery of fibulin-1 protects the basement membrane during cyclic stretching in C. elegans 按需递送的纤维蛋白-1在秀丽隐杆线虫的循环拉伸中保护基底膜

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-13 DOI: 10.1016/j.devcel.2025.07.015

Adam W.J. Soh, Michael R. Arnwine, Claire A. Gianakas, Zachary D. Clark, Qiuyi Chi, Erin J. Cram, Brenton D. Hoffman, David R. Sherwood

{"title":"On-demand delivery of fibulin-1 protects the basement membrane during cyclic stretching in C. elegans","authors":"Adam W.J. Soh, Michael R. Arnwine, Claire A. Gianakas, Zachary D. Clark, Qiuyi Chi, Erin J. Cram, Brenton D. Hoffman, David R. Sherwood","doi":"10.1016/j.devcel.2025.07.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.015","url":null,"abstract":"Basement membrane (BM) extracellular matrices enwrap and structurally support tissues. Whether BMs are uniquely constructed for tissues to undergo repetitive stretching and recoil events is unknown. During C. elegans ovulation, the spermathecal BM stretches ∼1.7-fold and then recoils to its original shape every 20 min to passage hundreds of oocytes. Fluorescence microscopy demonstrated that ovulating oocytes deliver the extracellular matrix protein fibulin-1 (FBL-1) through the spermathecal cell junctions to the BM during stretching, where it forms a dynamic overlapping network with type IV collagen. FBL-1 depletion led to a breakdown in type IV collagen and BM organization, resulting in a more deformable BM and extended spermatheca. Moreover, perturbation to FBL-1 network formation via mutagenesis was sufficient to disrupt tissue recoil and shape. Together, our study identifies an on-demand FBL-1 delivery system that protects the BM network when it is stretched, thereby allowing repeated rounds of tissue expansion and recovery.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"113 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825259","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

Dapk2 dysfunction leads to Mic60 lactylation and mitochondrial metabolic reprogramming, promoting lung cancer EGFR-TKI resistance and metastasis Dapk2功能障碍导致Mic60乳酸化和线粒体代谢重编程，促进肺癌EGFR-TKI耐药和转移

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-13 DOI: 10.1016/j.devcel.2025.07.014

Jie Zheng, Han She, Rui Han, Ju Tang, Yuanyao Dou, Conghua Lu, Daijuan Huang, Caiyu Lin, Di Wu, Chao He, Yunxia Du, Yinyu Wu, Yuxi Zhang, Chen Hu, Mengxiao Zhu, Yubo Wang, Qing Huang, Fan Wu, Yong He

{"title":"Dapk2 dysfunction leads to Mic60 lactylation and mitochondrial metabolic reprogramming, promoting lung cancer EGFR-TKI resistance and metastasis","authors":"Jie Zheng, Han She, Rui Han, Ju Tang, Yuanyao Dou, Conghua Lu, Daijuan Huang, Caiyu Lin, Di Wu, Chao He, Yunxia Du, Yinyu Wu, Yuxi Zhang, Chen Hu, Mengxiao Zhu, Yubo Wang, Qing Huang, Fan Wu, Yong He","doi":"10.1016/j.devcel.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.014","url":null,"abstract":"The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is often linked to tumor metastasis, making control of metastasis crucial. Here, we identified a critical signaling hub responsible for cancer metastasis and resistance development: mitochondrial cristae remodeling and metabolic reprogramming, using an anoikis-resistant cell model and a mouse tail vein metastasis model. EGFR-TKI-resistant cells exhibited stronger anoikis resistance (AR) and mitochondrial metabolism compared with sensitive cells, making them more prone to metastasis. Dysfunction of death-associated protein kinase 2 (Dapk2) altered Mic60 protein in mitochondrial cristae, increasing the abundance and compactness of the cristae and activating mitochondrial metabolism. Lactylation of the Mic60 protein may be the critical mechanism affecting the restructuring of mitochondrial cristae and activating mitochondrial metabolism. Our findings elucidate the role and underlying mechanisms of mitochondrial morphological dynamics and metabolic reprogramming in resistance and metastasis, offering potential therapeutic targets to overcome EGFR-TKI resistance and metastasis in lung cancer.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"18 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825262","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

PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism PINK1和PARK2通过控制线粒体铁介导的免疫代谢抑制胰腺肿瘤发生

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-07 DOI: 10.1016/j.devcel.2025.07.018

Changfeng Li, Ying Zhang, Xing Cheng, Hua Yuan, Shan Zhu, Jiao Liu, Qirong Wen, Yangchun Xie, Jinbao Liu, Guido Kroemer, Daniel J. Klionsky, Michael T. Lotze, Herbert J. Zeh, Rui Kang, Daolin Tang

引用次数: 0

Nuclear lamina phase separation orchestrates stress-induced transcriptional responses in plants 在植物中，核层相分离协调了胁迫诱导的转录反应

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-07 DOI: 10.1016/j.devcel.2025.07.008

Yu Tang, Xiao Liu, Yiling Fang, Enrico Calvanese, Yeram Hong, Yangnan Gu

{"title":"Nuclear lamina phase separation orchestrates stress-induced transcriptional responses in plants","authors":"Yu Tang, Xiao Liu, Yiling Fang, Enrico Calvanese, Yeram Hong, Yangnan Gu","doi":"10.1016/j.devcel.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.008","url":null,"abstract":"The nuclear lamina (NL), a perinuclear protein meshwork formed by nucleoskeleton and inner nuclear membrane (INM) proteins, is crucial for chromatin organization at the nuclear periphery and gene expression regulation in eukaryotic cells. However, NL-dependent transcriptional regulation remains poorly understood in plants due to the absence of most canonical NL proteins found in animals. Here, we report that the plant INM protein PLANT NUCLEAR ENVELOPE TRANSMEMBRANE 2 (PNET2) interacts with membrane-bound NAC (NAM, ATAF1/2, and CUC2) transcription factors, NTLs, via intrinsic disorder regions and promotes liquid-liquid phase separation within the NL. This compartmentalization effectively sequesters NTLs and restricts their transcriptional activity. In the absence of PNET2, NTLs become deregulated, triggering spontaneous and broad-spectrum stress responses. Importantly, we found that stress stimuli, such as heat shock, disrupt PNET2-NTL phase separation, releasing NTLs for target gene binding and transcriptional activation. These findings demonstrate a phase separation-based regulatory mechanism within the NL that controls membrane-bound transcription factor activity in response to environmental cues.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"27 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792328","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

Mechanochemical coupling of cell shape and organ function optimizes heart size and contractile efficiency in zebrafish 细胞形状和器官功能的机械化学耦合优化了斑马鱼的心脏大小和收缩效率

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-06 DOI: 10.1016/j.devcel.2025.07.011

Toby G.R. Andrews, Jake Cornwall-Scoones, Marie-Christine Ramel, Kirti Gupta, James Briscoe, Rashmi Priya

{"title":"Mechanochemical coupling of cell shape and organ function optimizes heart size and contractile efficiency in zebrafish","authors":"Toby G.R. Andrews, Jake Cornwall-Scoones, Marie-Christine Ramel, Kirti Gupta, James Briscoe, Rashmi Priya","doi":"10.1016/j.devcel.2025.07.011","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.011","url":null,"abstract":"How simple tissue primordia sculpt complex functional organs, robustly and reproducibly, remains elusive. During zebrafish development, the embryonic myocardial wall matures into an intricate 3D architecture, composed of an outer compact layer enveloping an inner layer of multicellular trabecular ridges. How these tissue layers acquire their characteristic form suited for their function remains an open question. Here, we find that multiscale mechanochemical coupling and an emergent tissue-scale morphological transition steer functional maturation of the developing zebrafish heart. Single-celled trabecular seeds recruit outer compact layer cells to mature into clonally heterogeneous multicellular ridges, thereby amplifying cardiac contractile forces. In response, the remaining compact layer cells are stretched, which impedes their further recruitment, thereby constraining trabecular ridge density. Concomitantly, Notch-dependent actomyosin dampening triggers a sharp transition in myocardial tissue area, activating rapid organ growth that expands blood-filling capacity. Thus, multiscale self-organizing interactions optimize heart size and contractile efficiency to support embryonic life.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"15 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787452","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 extracellular-matrix-remodeling capability exposes therapeutic vulnerability in a subset of renal cell carcinomas with tumor thrombi 细胞外基质重塑能力暴露了一类肾细胞癌伴肿瘤血栓的治疗脆弱性

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-06 DOI: 10.1016/j.devcel.2025.07.010

Qi Zhang, Yezhen Tan, Qiyang Liang, Liangyou Gu, Yue Shi, Yan Huang, Xiubin Li, Jie Qi, Cheng Peng, Hanfeng Wang, Yaohui Wang, Kan Liu, Tianwei Cai, Yudan He, Qingbo Huang, Xu Zhang, Baojun Wang, Xin Ma, Weimin Ci

{"title":"The extracellular-matrix-remodeling capability exposes therapeutic vulnerability in a subset of renal cell carcinomas with tumor thrombi","authors":"Qi Zhang, Yezhen Tan, Qiyang Liang, Liangyou Gu, Yue Shi, Yan Huang, Xiubin Li, Jie Qi, Cheng Peng, Hanfeng Wang, Yaohui Wang, Kan Liu, Tianwei Cai, Yudan He, Qingbo Huang, Xu Zhang, Baojun Wang, Xin Ma, Weimin Ci","doi":"10.1016/j.devcel.2025.07.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.010","url":null,"abstract":"Preoperative downstaging of renal cell carcinoma with a tumor thrombus (RCC-TT) makes thrombectomy feasible. However, treatment resistance is common and may partly be attributed to the tumor-promoting role of the tumor microenvironment (TME). Herein, we sequenced, integrated, and comprehensively analyzed multi-center, multi-omics data from 164 RCC-TT patients and identified two clinically relevant RCC-TT subtypes. We find that the poor-prognosis subtype (TT1) exhibits enhanced extracellular-matrix (ECM) remodeling driven by epithelial LOX expression. Spatial transcriptomics (ST) shows the co-localization of GPNMB+ macrophages, THBS2+ fibroblasts, and LOX+ malignant cells around tumor nests in TT1 tumors, reinforcing tumor immune barriers (TIBs). Our extensive validations using cell lines, syngeneic mouse models, multiplex immunofluorescence staining, and large-scale RCC cohorts underscore the potential of LOX inhibition in disrupting TIBs, sensitizing RCC to immunotherapy, and overcoming treatment-induced phenotypic plasticity. This study provides insights into the biological underpinnings and prognosis assessment of RCC-TT, demonstrating targetable ECM-remodeling vulnerabilities.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"52 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787662","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

A cholesterol-dependent switch controls organ-specific metastasis in pancreatic cancer 一种胆固醇依赖性开关控制胰腺癌的器官特异性转移

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-04 DOI: 10.1016/j.devcel.2025.07.001

Julie Haenlin, Almut Schulze

引用次数: 0

PRC2-mediated repression of PIF4 targets beyond the on/off switch of gene expression prc2介导的PIF4抑制目标超出了基因表达的开/关开关

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-08-04 DOI: 10.1016/j.devcel.2025.07.005

Zhe Wu

引用次数: 0