{"title":"Nucleolar protein PEXF controls ribosomal RNA synthesis and pluripotency exit","authors":"Zihao Li, Siwen Chen, Sifang Li, Hua Chao, Wenjun Hao, Shuai Zhang, Zemin Li, Jianru Wang, Xiang Li, Yong Wan, Hui Liu","doi":"10.1016/j.devcel.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.004","url":null,"abstract":"Maintenance and exit from pluripotency of embryonic stem cells (ESCs) are controlled by highly coordinated processes of protein synthesis and ribosome biogenesis (RiBi). ESCs are characterized by low rates of global protein synthesis and high levels of RiBi. Transient reduction of RiBi is a characteristic molecular event during the exit from pluripotency, of which the regulatory mechanism is unclear. Here, we identify that a previously uncharacterized nucleolar protein, pluripotency exit factor (PEXF), encoded by long noncoding RNA <em>LINC00472</em>, plays a role in the transient reduction of RiBi. PEXF dissociates RNA polymerase I from the rDNA through interaction with the rDNA promoter region in a liquid-liquid phase separation-dependent manner, therefore inhibiting the production of pre-ribosomal RNA, a key component of ribosomes. This finding reveals a potential mechanism of exit from pluripotency gated by ribosome levels in human ESCs.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"41 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886696","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 : 2024-12-26DOI: 10.1016/j.devcel.2024.12.005
David Remy, Sandra Antoine-Bally, Sophie de Toqueville, Célia Jolly, Anne-Sophie Macé, Gabriel Champenois, Fariba Nemati, Isabel Brito, Virginie Raynal, Amulya Priya, Adèle Berlioz, Ahmed Dahmani, André Nicolas, Didier Meseure, Elisabetta Marangoni, Philippe Chavrier
{"title":"TFEB triggers a matrix degradation and invasion program in triple-negative breast cancer cells upon mTORC1 repression","authors":"David Remy, Sandra Antoine-Bally, Sophie de Toqueville, Célia Jolly, Anne-Sophie Macé, Gabriel Champenois, Fariba Nemati, Isabel Brito, Virginie Raynal, Amulya Priya, Adèle Berlioz, Ahmed Dahmani, André Nicolas, Didier Meseure, Elisabetta Marangoni, Philippe Chavrier","doi":"10.1016/j.devcel.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.005","url":null,"abstract":"The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently hyperactivated in triple-negative breast cancers (TNBCs) associated with poor prognosis and is a therapeutic target in breast cancer management. Here, we describe the effects of repression of mTOR-containing complex 1 (mTORC1) through knockdown of several key mTORC1 components or with mTOR inhibitors used in cancer therapy. mTORC1 repression results in an ∼10-fold increase in extracellular matrix proteolytic degradation. Repression in several TNBC models, including in patient-derived xenografts (PDXs), induces nuclear translocation of transcription factor EB (TFEB), which drives a transcriptional program that controls endolysosome function and exocytosis. This response triggers a surge in endolysosomal recycling and the surface exposure of membrane type 1 matrix metalloproteinase (MT1-MMP) associated with invadopodia hyperfunctionality. Furthermore, repression of mTORC1 results in a basal-like breast cancer cell phenotype and disruption of ductal carcinoma <em>in situ</em> (DCIS)-like organization in a tumor xenograft model. Altogether, our data call for revaluation of mTOR inhibitors in breast cancer therapy.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"31 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887055","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 : 2024-12-26DOI: 10.1016/j.devcel.2024.11.022
Vidur Garg, Yang Yang, Sonja Nowotschin, Manu Setty, Eralda Salataj, Ying-Yi Kuo, Dylan Murphy, Roshan Sharma, Amy Jang, Alexander Polyzos, Dana Pe’er, Effie Apostolou, Anna-Katerina Hadjantonakis
{"title":"Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice","authors":"Vidur Garg, Yang Yang, Sonja Nowotschin, Manu Setty, Eralda Salataj, Ying-Yi Kuo, Dylan Murphy, Roshan Sharma, Amy Jang, Alexander Polyzos, Dana Pe’er, Effie Apostolou, Anna-Katerina Hadjantonakis","doi":"10.1016/j.devcel.2024.11.022","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.11.022","url":null,"abstract":"Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells—<em>in vitro</em> counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions. While GATA4-mediated ES-to-iXEN conversion was rapid and nearly deterministic, OCT4-, KLF4-, and SOX2-induced XEN-to-induced pluripotent stem (iPS) reprogramming progressed with diminished efficiency and kinetics. A dominant PrE transcriptional program, safeguarded by GATA4, alongside elevated chromatin accessibility and reduced DNA methylation of the EPI underscored the differential plasticities of the two states. Mapping <em>in vitro</em> to embryo trajectories tracked reprogramming cells in either direction along EPI and PrE <em>in vivo</em> states, without transitioning through the ICM.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886697","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":"Natural variation in an HD-ZIP factor identifies its role in controlling apple leaf cuticular wax deposition","authors":"Fuguo Cao, Qian Qian, Zhongxing Li, Jingrong Wang, Zeyuan Liu, Zitong Zhang, Chundong Niu, Yinpeng Xie, Fengwang Ma, Qingmei Guan","doi":"10.1016/j.devcel.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.001","url":null,"abstract":"Natural variation is an invaluable genetic resource for plant trait improvement. Here, we performed a genome-wide association study (GWAS) analysis and identified MdHDG5, which controls apple leaf cuticular wax. An A-to-G single-nucleotide polymorphism (SNP) on the <em>HDG5</em> promoter is associated with <em>HDG5</em> expression and hexacosanol content (a component of leaf cuticular wax). Furthermore, the single-nucleotide variation (G/G) within a MYB <em>cis</em>-regulatory element (CRE) can be directly bound by MYB62, which represses <em>HDG5</em> expression and leaf wax deposition. In addition, MdPIAL2, a Small Ubiquitin-like Modifier (SUMO) E3 ligase, positively controls apple leaf wax deposition by stabilizing MdHDG5, while MdMIEL1 interacts with and degrades both MdHDG5 and MdPIAL2 to negatively control leaf wax deposition. Notably, <em>MIEL1</em> expression is negatively associated with leaf hexacosanol deposition. Taken together, our results provide significant genetic insights into the natural variation of leaf cuticular wax loads in apple and identify the intricate molecular regulation of MdHDG5.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"113 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880112","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 : 2024-12-24DOI: 10.1016/j.devcel.2024.12.003
Daniel J. Salas-Escabillas, Megan T. Hoffman, Sydney M. Brender, Jacee S. Moore, Hui-Ju Wen, Simone Benitz, Erick T. Davis, Daniel Long, Allison M. Wombwell, Ella Rose D. Chianis, Brittany L. Allen-Petersen, Nina G. Steele, Rosalie C. Sears, Ichiro Matsumoto, Kathleen E. DelGiorno, Howard C. Crawford
{"title":"Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer","authors":"Daniel J. Salas-Escabillas, Megan T. Hoffman, Sydney M. Brender, Jacee S. Moore, Hui-Ju Wen, Simone Benitz, Erick T. Davis, Daniel Long, Allison M. Wombwell, Ella Rose D. Chianis, Brittany L. Allen-Petersen, Nina G. Steele, Rosalie C. Sears, Ichiro Matsumoto, Kathleen E. DelGiorno, Howard C. Crawford","doi":"10.1016/j.devcel.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.003","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown. To determine the fate of mTCs during PDA progression, we created a dual recombinase lineage trace model, wherein a pancreas-specific FlpO was used to induce tumorigenesis, while a tuft-cell specific Pou2f3<sup>CreERT/+</sup> driver was used to induce expression of a tdTomato reporter. We found that mTCs in carcinoma transdifferentiate into neural-like progenitor cells (NRPs), a cell type associated with poor survival in patients. Using conditional knockout and overexpression systems, we found that <em>Myc</em> activity in mTCs is necessary and sufficient to induce this tuft-to-neuroendocrine transition (TNT).","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"20 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880238","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 : 2024-12-24DOI: 10.1016/j.devcel.2024.12.002
Fergus Tollervey, Manolo U. Rios, Evgenia Zagoriy, Jeffrey B. Woodruff, Julia Mahamid
{"title":"Molecular architectures of centrosomes in C. elegans embryos visualized by cryo-electron tomography","authors":"Fergus Tollervey, Manolo U. Rios, Evgenia Zagoriy, Jeffrey B. Woodruff, Julia Mahamid","doi":"10.1016/j.devcel.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.002","url":null,"abstract":"Centrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by pericentriolar material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and spindle microtubule formation remain unanswered, partly due to limited availability of molecular-resolution structural data inside cells. Here, we use cryo-electron tomography to visualize centrosomes across the cell cycle in cells isolated from <em>C. elegans</em> embryos. We describe a pseudo-timeline of centriole assembly and identify distinct structural features in both mother and daughter centrioles. We find that centrioles and PCM microtubules differ in protofilament number (13 versus 11), which could be explained by atypical γ-tubulin ring complexes with 11-fold symmetry identified at the minus ends of short PCM microtubule segments. We further characterize a porous and disordered network that forms the interconnected PCM. Thus, our work builds a three-dimensional structural atlas that helps explain how centrosomes assemble, grow, and achieve function.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880108","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 : 2024-12-19DOI: 10.1016/j.devcel.2024.11.021
Sural K. Ranamukhaarachchi, Alyssa Walker, Man-Ho Tang, William D. Leineweber, Sophia Lam, Wouter-Jan Rappel, Stephanie I. Fraley
{"title":"Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells","authors":"Sural K. Ranamukhaarachchi, Alyssa Walker, Man-Ho Tang, William D. Leineweber, Sophia Lam, Wouter-Jan Rappel, Stephanie I. Fraley","doi":"10.1016/j.devcel.2024.11.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.11.021","url":null,"abstract":"The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM. Matrix-remodeling activity by matrix metalloproteinases (MMPs) is localized to the base of protrusions in cells that initiate ICM, whereas RCM does not require MMPs and is associated with ITGβ1-mediated remodeling localized globally around the cell body. Further analysis <em>in vitro</em> and <em>in vivo</em> supports the concept that distinct matrix-remodeling strategies encode collective migration behaviors and tissue structure.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"113 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849565","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":"The plant signal peptide CLE7 induces plant defense response against viral infection in Nicotiana benthamiana","authors":"Peng Liu, Juan Zhang, Shuang Liu, Yaoyao Li, Chunyan Qi, Qitao Mo, Yaoyao Jiang, Haichao Hu, Tianye Zhang, Kaili Zhong, Jianqian Liu, Qiansheng Liao, Jianping Chen, Jian Yang","doi":"10.1016/j.devcel.2024.11.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.11.020","url":null,"abstract":"In plants, small peptides are important players in the plant stress response, yet their function in plant antiviral responses remains poorly understood. Here, we identify that the plant small peptide, CLAVATA3/ESR-RELATED 7 (CLE7), enhances plant resistance to Chinese wheat mosaic virus infection in <em>Nicotiana (N.) benthamiana</em>. Subsequent investigations demonstrate that CLE7 recognizes receptor kinase NbPXC3 to control the plant antiviral response. Moreover, CLE7-NbPXC3 signaling induces NbMKK2-controlled NbMPK4 phosphorylation, resulting in phosphorylation of the transcription factor NbEDT1. NbEDT1 phosphorylation is involved in the transcriptional activity of <em>NbNCED3</em>, which is a rate-limiting enzyme in abscisic acid (ABA) biosynthesis. Moreover, CLE7 activates broad-spectrum disease resistance to multiple RNA viral infections. Our study indicates that CLE7 induces a plant antiviral response through a series of immune signal transductions in <em>N. benthamiana</em> and provides a foundation for the exploration of efficient viral disease management methods based on plant small peptides.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"28 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825708","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 : 2024-12-16DOI: 10.1016/j.devcel.2024.11.012
Marie-Pierre Junier, Elias A. El-Habr
{"title":"Emergence of the cell-matrix adhesion element ILK as a player in glioblastoma cell plasticity","authors":"Marie-Pierre Junier, Elias A. El-Habr","doi":"10.1016/j.devcel.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.11.012","url":null,"abstract":"Glioblastoma cells exhibit remarkable plasticity, enabling them to adapt to environmental cues and transition through various developmental-like states with distinct properties. In this issue of <em>Developmental Cell</em>, Loftus et al. identify ILK as an intrinsic regulator of glioblastoma cell transitions between progenitor-like and mesenchymal/astrocyte-like states.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"18 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825703","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 : 2024-12-16DOI: 10.1016/j.devcel.2024.11.004
Cédric Schindfessel, Steffen Vanneste
{"title":"Endoplasmic reticulum-anchored proteins in control of AUXIN RESPONSE FACTOR condensation","authors":"Cédric Schindfessel, Steffen Vanneste","doi":"10.1016/j.devcel.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.11.004","url":null,"abstract":"Sequestration of AUXIN RESPONSE FACTOR (ARF) transcription factors in cytoplasmic condensates represents a specialized mechanism for modulating cellular auxin responsiveness. In this issue of <em>Developmental Cell</em>, Xuan et al. show that MULTIPLE C2-DOMAIN AND TRANSMEMBRANE REGION PROTEIN (MCTP) proteins stimulate lateral root development by antagonizing ARF7 and ARF19 condensation.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"14 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825710","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}