European journal of cell biology最新文献

{"title":"Evolution of organoid genetics","authors":"Thomas M. Klompstra ,&nbsp;Ki-Jun Yoon ,&nbsp;Bon-Kyoung Koo","doi":"10.1016/j.ejcb.2025.151481","DOIUrl":"10.1016/j.ejcb.2025.151481","url":null,"abstract":"<div><div>Organoids have revolutionized <em>in vitro</em> research by offering three-dimensional, multicellular systems that recapitulate the structure, function, and genetics of human tissues. Initially developed from both pluripotent stem cells (PSCs) and adult stem cells (AdSCs), organoids have expanded to model nearly every major human organ, significantly advancing developmental biology, disease modeling, and therapeutic screening. This review highlights the progression of organoid technologies, emphasizing the integration of genetic tools, including CRISPR-Cas9, prime editing, and lineage tracing. These advancements have facilitated precise modeling of human-specific pathologies and drug responses, often surpassing traditional 2D cultures and animal models in accuracy. Emerging technologies, such as organoid fusion, xenografting, and optogenetics, are expected to further enhance our understanding of cellular interactions and microenvironmental dynamics. As organoid complexity and genetic engineering methods continue to evolve, they will become increasingly indispensable for personalized medicine and translational research, bridging gaps between <em>in vitro</em> and <em>in vivo</em> systems.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151481"},"PeriodicalIF":4.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient pharmacological inhibition of SUMOylation during pregnancy induces craniofacial malformations in offspring mice","authors":"Jorge Mata-Garrido ,&nbsp;Isabella Zafferri ,&nbsp;Alice Nordlinger ,&nbsp;Yann Loe-Mie ,&nbsp;Anne Dejean ,&nbsp;Jack-Christophe Cossec","doi":"10.1016/j.ejcb.2025.151480","DOIUrl":"10.1016/j.ejcb.2025.151480","url":null,"abstract":"<div><div>Cell identity plays a pivotal role in embryo development, guiding the process of cellular differentiation essential for tissue and organ formation. Post-translational modification by the ubiquitin-related SUMO protein acts as a chromatin barrier to cell fate conversions. While SUMOylation deficiency is incompatible with mammalian embryonic development, haploinsufficiency for the SUMOylation machinery's E1 enzyme, UBA2, leads to various phenotypic traits in humans, including craniofacial malformations and aplasia cutis congenita. To investigate SUMO's role in organogenesis, SUMOylation was transiently suppressed using a specific pharmacological inhibitor, TAK981, administered during the early post-implantation embryo stage. A high-concentration injection led to embryonic lethality associated with epigenetic scars and alterations in nuclear and nucleolar integrity observed in treated embryo-derived fibroblasts. Lower-concentration injections resulted in viable mice with craniofacial deformities often accompanied by hydrocephalus, syndactyly and an aplasia cutis-like phenotype. Transcriptomic analysis revealed the repression of genes involved in neural crest differentiation in the TAK981-treated embryos as well as the overexpression of the <em>Fgfr</em> gene family in the adult TAK981 progeny. These genes, expressed in neural crest derivatives, are known for their gain-of-function mutations linked to human craniosynostosis syndromes, suggesting that potential overactivation of the FGF signaling pathway may contribute to the malformations observed in TAK981 progeny. Altogether, disruption of the SUMOylation/deSUMOylation equilibrium during a short embryonic period is sufficient to induce persistent cellular defects and transcriptional alterations, resulting in severe offspring malformations. In conclusion, the SUMO inhibitor TAK981 has teratogenic effects, disrupting normal fetal development and causing congenital disabilities reminiscent of traits observed in UBA2-related syndrome.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151480"},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse colorectal cancer organoids: Lessons from syngeneic and orthotopic transplantation systems","authors":"Yu Muta,&nbsp;Yuki Nakanishi","doi":"10.1016/j.ejcb.2025.151478","DOIUrl":"10.1016/j.ejcb.2025.151478","url":null,"abstract":"<div><div>Colorectal cancer (CRC) organoids provide more accurate and tissue-relevant models compared to conventional two-dimensional cultured cell cultures. Mouse CRC organoids, in particular, offer unique advantages over their human counterparts, as they can be transplanted into immunocompetent mice. These syngeneic transplantation models create a robust system for studying cancer biology in the immunocompetent tumor microenvironment (TME). This article discusses the development and applications of these organoid systems, emphasizing their capacity to faithfully recapitulate <em>in vivo</em> tumor progression, metastasis, and the immune landscape.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151478"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143211976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids","authors":"Tatsuya Inui ,&nbsp;Yusei Uraya ,&nbsp;Yukiko Ueyama-Toba ,&nbsp;Hiroyuki Mizuguchi","doi":"10.1016/j.ejcb.2025.151479","DOIUrl":"10.1016/j.ejcb.2025.151479","url":null,"abstract":"<div><div>To evaluate the intestinal absorption and metabolism of orally administered drugs, human induced pluripotent stem (iPS) cell‑derived enterocyte‑like cells (ELCs) are expected to be useful. In a previous report, we succeeded in developing a highly functional monolayer platform (ELC-org-mono) from human iPS cell-derived ELCs through an organoid culture and demonstrated its suitability for pharmacokinetic studies. In recent years, the air–liquid interface (ALI) culture model was developed, allowing for the culture of epithelial tissue under conditions that mimic the in vivo environment. In the present study, we applied ALI culture to ELC-org-mono for further improvement of intestinal functions. ALI culture of ELC-org-mono greatly developed goblet cells and enhanced the gene expression levels of many drug-metabolizing enzymes, drug transporters and intestinal differentiation markers. However, their activities were not enhanced. RNA-seq analysis suggested that ALI culture increased the expression of genes related to metabolic processes but decreased glycolytic processes. Analysis of glycolytic capacity confirmed that ALI culture decreased glycolytic activities. Thus, there is room for some adjustment in the ALI culture model to optimize its applicability to pharmacokinetic studies using ELC-org-mono.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151479"},"PeriodicalIF":4.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143347848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitronectin regulates focal adhesion turnover and migration of human placenta-derived MSCs under nutrient stress","authors":"Srishti Dutta Gupta,&nbsp;Nitish Pal,&nbsp;Malancha Ta","doi":"10.1016/j.ejcb.2025.151477","DOIUrl":"10.1016/j.ejcb.2025.151477","url":null,"abstract":"<div><div>At sites of tissue damage and wound healing, the mesenchymal stem cells (MSCs) are often challenged by nutrient availability due to blood supply disruption. Thus, it becomes critical to identify novel factors and their mechanism of action in regulating the adhesion and migration of MSCs under nutrient stress condition for successful clinical application. In human placenta-derived MSCs (PL-MSCs), we demonstrated an increase in cell spread area, along with increased adhesion and reduced migration of the cells, when cultured under nutrient stress condition. Correspondingly, an increase in the total number per cell and size of focal adhesions (FAs), together with prominent stress fibers were observed in nutrient-stressed PL-MSCs compared to control PL-MSCs. The FAs were demonstrated to be more stable, exhibiting slower turnover and longer lifespan. Vitronectin (VTN), an ECM glycoprotein, was upregulated under nutrient stress condition. Knockdown of VTN in PL-MSCs led to a significant reduction in the total number per cell and size of FAs, along with their faster turnover and shorter lifespan. Subsequently, a reversal in the cell spread area, adhesion and migration properties of the nutrient-stressed PL-MSCs were noted. Additionally, our findings indicated that VTN, as an upstream regulator, stimulated the phosphorylation of myosin light chain, which possibly promoted the maturation and stability of FAs along with assembly of stress fibers, thereby leading to increased adhesion and reduced migration of the cells. Overall, our study defines a distinct role of VTN as a critical regulator of migration in PL-MSCs under nutrient stress condition.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151477"},"PeriodicalIF":4.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in intestinal organoid technology featuring an open apical surface","authors":"Ye Chen ,&nbsp;Yi Wang","doi":"10.1016/j.ejcb.2025.151476","DOIUrl":"10.1016/j.ejcb.2025.151476","url":null,"abstract":"<div><div>Since the development of the three-dimensional (3D) “mini-gut” culture system, adult stem cell-derived organoid technology has rapidly advanced, providing <em>in vitro</em> models that replicate key cellular, molecular, and physiological properties of multiple organs. The 3D intestinal organoid system has resolved many long-standing challenges associated with immortalized or cancer cell cultures, offering unparalleled capabilities for modeling gastrointestinal development and diseases. However, significant limitations remain, including restricted accessibility to the epithelial apical surface for studying host-microbe interactions, interruptions in modeling chronic gastrointestinal diseases due to frequent passaging and dissociation, and the absence of mechanical cues such as peristalsis and luminal flow, which are critical for organ development and function. To address these challenges, recent advancements have introduced Transwell-based monolayer cultures and microfluidic device-based technologies including “organ-on-a-chip” and scaffold-guided 'mini-gut' system. This review highlights these innovations, with a focus on adult stem cell-derived intestinal organoid models that feature an open apical surface and discusses their prospects and challenges for advancing basic research and clinical applications.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151476"},"PeriodicalIF":4.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRP1 involvement in FHIT-regulated HER2 signaling in non-small cell lung cancer","authors":"Théophile Ponchel ,&nbsp;Emma Loeffler ,&nbsp;Julien Ancel ,&nbsp;Audrey Brisebarre ,&nbsp;Nathalie Lalun ,&nbsp;Véronique Dalstein ,&nbsp;Anne Durlach ,&nbsp;Gaëtan Deslée ,&nbsp;Stéphane Dedieu ,&nbsp;Myriam Polette ,&nbsp;Béatrice Nawrocki-Raby","doi":"10.1016/j.ejcb.2024.151475","DOIUrl":"10.1016/j.ejcb.2024.151475","url":null,"abstract":"<div><div>The tumor suppressor fragile histidine triad (FHIT) is frequently lost in non-small cell lung cancer (NSCLC). We previously showed that a down-regulation of FHIT causes an up-regulation of the activity of HER2 associated to an epithelial-mesenchymal transition (EMT) and that lung tumor cells harboring a FHIT^low/pHER2^high phenotype are sensitive to anti-HER2 drugs. Here, we sought to decipher the FHIT-regulated HER2 signaling pathway in NSCLC. Transcriptomic analysis of tumor cells isolated from NSCLC revealed the endocytic receptor low density lipoprotein receptor-related protein 1 (LRP1), a central regulator of membrane trafficking and cell signaling, as a potential player of this signaling. In a cohort of 80 NSCLC assessed by immunohistochemistry, we found a significant association between a low FHIT expression and a high pHER2 and LRP1 expression by tumor cells. Experiments of FHIT silencing showed that FHIT regulated LRP1 expression both at the mRNA and protein levels in lung cell lines. Analyzing the relationship between LRP1 and HER2, we observed that an anti-HER2 targeted therapy reversed LRP1 overexpression induced by FHIT silencing whereas LRP1 silencing did not affect HER2 activity. Studying the functional role of LRP1, we showed that cell proliferation and invasion induced by FHIT silencing were LRP1-dependent. In addition, we found that the induction of vimentin upon FHIT inactivation was counteracted by LRP1 silencing. These results suggest that LRP1 acts downstream of HER2 to induce EMT and tumor progression following FHIT loss. Dual targeting of HER2 and LRP1 might represent a therapeutic strategy to more efficiently inhibit HER2 signaling in FHIT-negative NSCLC.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151475"},"PeriodicalIF":4.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal organoids: The path towards clinical application","authors":"Hady Yuki Sugihara,&nbsp;Ryuichi Okamoto,&nbsp;Tomohiro Mizutani","doi":"10.1016/j.ejcb.2024.151474","DOIUrl":"10.1016/j.ejcb.2024.151474","url":null,"abstract":"<div><div>Organoids have revolutionized the whole field of biology with their ability to model complex three-dimensional human organs <em>in vitro</em>. Intestinal organoids were especially consequential as the first successful long-term culture of intestinal stem cells, which raised hopes for translational medical applications. Despite significant contributions to basic research, challenges remain to develop intestinal organoids into clinical tools for diagnosis, prognosis, and therapy. In this review, we outline the current state of translational research involving adult stem cell and pluripotent stem cell derived intestinal organoids, highlighting the advances and limitations in disease modeling, drug-screening, personalized medicine, and stem cell therapy. Preclinical studies have demonstrated a remarkable functional recapitulation of infectious and genetic diseases, and there is mounting evidence for the reliability of intestinal organoids as a patient-specific avatar. Breakthroughs now allow the generation of structurally and cellularly complex intestinal models to better capture a wider range of intestinal pathophysiology. As the field develops and evolves, there is a need for standardized frameworks for generation, culture, storage, and analysis of intestinal organoids to ensure reproducibility, comparability, and interpretability of these preclinical and clinical studies to ultimately enable clinical translation.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151474"},"PeriodicalIF":4.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries","authors":"Javier Abello ,&nbsp;Ying Yin ,&nbsp;Yonghui Zhao ,&nbsp;Josh Maurer ,&nbsp;Jihui Lee ,&nbsp;Cherokee Bodell ,&nbsp;Jahmiera Richee ,&nbsp;Abigail J. Clevenger ,&nbsp;Zarek Burton ,&nbsp;Megan E. Goeckel ,&nbsp;Michelle Lin ,&nbsp;Stephanie Grainger ,&nbsp;Carmen M. Halabi ,&nbsp;Shreya A. Raghavan ,&nbsp;Rajan Sah ,&nbsp;Amber N. Stratman","doi":"10.1016/j.ejcb.2024.151473","DOIUrl":"10.1016/j.ejcb.2024.151473","url":null,"abstract":"<div><div>Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating <em>klf2a,</em> a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed <em>klf2a</em> and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased <em>klf2a</em> levels and decreased vSMC association with arteries. We supported the small molecule findings with <em>in vivo</em> genetic suppression of <em>piezo1</em> and <em>2</em> in zebrafish, resulting in loss of <em>transgelin+</em> vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific <em>Piezo1</em> knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine the underlying mechanism, we used <em>in vitro</em> modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151473"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholangiocyte organoids for disease, cancer, and regenerative medicine","authors":"Munemasa Nagao ,&nbsp;Akihisa Fukuda ,&nbsp;Hirotaka Kashima ,&nbsp;Sho Matsuyama ,&nbsp;Kei Iimori ,&nbsp;Shinnosuke Nakayama ,&nbsp;Kenta Mizukoshi ,&nbsp;Munenori Kawai ,&nbsp;Go Yamakawa ,&nbsp;Mayuki Omatsu ,&nbsp;Mio Namikawa ,&nbsp;Tomonori Masuda ,&nbsp;Yukiko Hiramatsu ,&nbsp;Yu Muta ,&nbsp;Takahisa Maruno ,&nbsp;Yuki Nakanishi ,&nbsp;Tatsuaki Tsuruyama ,&nbsp;Hiroshi Seno","doi":"10.1016/j.ejcb.2024.151472","DOIUrl":"10.1016/j.ejcb.2024.151472","url":null,"abstract":"<div><div>The biliary tract is a ductal network comprising the intrahepatic (IHBDs) and extrahepatic bile duct (EHBDs). Biliary duct disorders include cholangitis, neoplasms, and injury. However, the underlying mechanisms are not fully understood. With advancements in 3D culture technology, cholangiocyte organoids (COs) derived from primary tissues or induced pluripotent stem cells (iPSCs) can accurately replicate the structural and functional properties of biliary tissues. These organoids have become powerful tools for studying the pathogenesis of biliary diseases, such as cystic fibrosis and primary sclerosing cholangitis, and for developing new therapeutic strategies for cholangiocarcinoma. Additionally, COs have the potential to repair bile duct injuries and facilitate transplantation therapies. This review also discusses the use of organoids in genetically engineered mouse models to provide mechanistic insights into tumorigenesis and cancer progression. Continued innovation and standardization of organoid technology are crucial for advancing precision medicine for biliary diseases and cancer.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151472"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}