European journal of cell biology最新文献

{"title":"Activity and function of auxiliary fluxes of glucose metabolism in response to physiological normoxia (5 % O2) during long-term Adipose-Derived Stem/Stromal cell culture","authors":"Paulina Rybkowska ,&nbsp;Maria Kawalec ,&nbsp;Dorota Dymkowska ,&nbsp;Klaudia Radoszkiewicz ,&nbsp;Barbara Zabłocka ,&nbsp;Krzysztof Zabłocki ,&nbsp;Anna Sarnowska","doi":"10.1016/j.ejcb.2025.151486","DOIUrl":"10.1016/j.ejcb.2025.151486","url":null,"abstract":"<div><div>Energy metabolism homeostasis emerges as a dominant element influencing mesenchymal stem/stromal cells’ trajectory of development. The predominant glycolysis activity is a primary driver of cell proliferation and maintenance of the high-energetic state. Here, we examined the functions of two crucial auxiliary pathways: the phosphate-pentose pathway (PPP) and fructose-2,6-biphosphate pathway (FBP) to evaluate their impact on the therapeutic potential of Adipose-Derived Stem/Stromal cells (ASCs) during prolonged culture in various oxygen conditions: 5 % O₂ - physiological normoxia or 21 % O₂ - atmospheric oxygen. Our findings demonstrate that ASCs cultured in 5 % O₂ increased the rate of proliferation, migration, and expression of stemness factors, which is prominent during the initial and middle passages. Additionally, ASCs cultured in a 5 % O₂ exhibited heightened protection mechanisms against free radicals, increased LDH gene expression, and elevated extracellular acidification rate (ECAR). By estimating the HIF-1α level, we concluded that 5 % oxygen conditions were insufficient to induce a profound hypoxic state in ASCs. However, at the protein level, both the PPP and FBP pathways appeared to be more active in young (2-passage) cells, regardless of oxygen conditions, and their activity diminished over time. Additionally, the chemical suppression of G6PDH by Polydatin and inhibition of PFKFB3 by PFK-158 in ASCs (passage-2) revealed dose- and time-dependent effect on decreasing migratory capabilities of cells. Nevertheless, our work underscores the adaptable nature of ASC metabolism to prevailing external conditions, with the aging of the culture contributing to the decline in glycolysis-associated auxiliary pathways.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151486"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767181","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":"Advances in modeling the Charcot-Marie-Tooth disease: Human induced pluripotent stem cell-derived Schwann cells harboring SH3TC2 variants","authors":"Camille Loret ,&nbsp;Camille Scherrer ,&nbsp;Amandine Rovini ,&nbsp;Ioanna Pyromali ,&nbsp;Pierre-Antoine Faye ,&nbsp;Angélique Nizou ,&nbsp;Franck Sturtz ,&nbsp;Frédéric Favreau ,&nbsp;Anne-Sophie Lia","doi":"10.1016/j.ejcb.2025.151485","DOIUrl":"10.1016/j.ejcb.2025.151485","url":null,"abstract":"<div><div>Human induced pluripotent stem cells (hiPSCs) represent a powerful tool for investigating neuropathological disorders, such as Charcot-Marie-Tooth disease (CMT), the most prevalent inherited peripheral neuropathy, where the cells of interest are hardly accessible. Advancing the development of appropriate cellular models is crucial for studying the disease’s pathophysiology. In this study, we present the first two isogenic hiPSC-derived Schwann cell models for studying CMT4C, also known as AR-CMTde-<em>SH3TC2</em>. This subtype of CMT is associated with alterations in <em>SH3TC2</em> and is the most prevalent form of autosomal recessive demyelinating CMT. We aimed to study the impact of two nonsense mutations in <em>SH3TC2</em>. To achieve this, we used two CRISPR hiPSC clones, one carrying a homozygous nonsense mutation: c.211C&gt;T, p.Gln71*, and the other one, carrying the most common AR-CMTde-<em>SH3TC2</em> alteration, c.2860G&gt;A, p.Arg954*. To study the endogenous expression of SH3TC2 in the cells mainly altered in AR-CMTde-<em>SH3TC2</em>, we initiated the differentiation of both our CMT clones and their isogenic control into Schwann cells (SCs). This study represents the first <em>in vitro</em> investigation of human endogenous SH3TC2 expression in AR-CMTde-<em>SH3TC2</em> hiPSC-derived SC models, allowing for the examination of its expression and of its cellular impact. By comparing this AR-CMTde-<em>SH3TC2</em> models to the control one, we observed disparities in RNA and protein expression of SH3TC2. Additionally, our RNA and coculture experiments with hiPSC-derived motor neurons (MNs) revealed delayed maturation of SCs and a reduced ability of SH3TC2-deficient SCs to sustain motor neuron culture. Our findings also demonstrated a disability in receptor recycling in SH3TC2-deficient cells, depending on the AR-CMTde-<em>SH3TC2</em> alteration. These hiPSC-derived-SC models further provide a new modelling tool for studying Schwann cell contribution to CMT4C.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151485"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705375","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":"iPSC screening identifies CACNA2D2 as a potential therapeutic target for FTLD-Tau","authors":"Keiko Imamura ,&nbsp;Ayako Nagahashi ,&nbsp;Aya Okusa ,&nbsp;Tomoki Sakasai ,&nbsp;Kayoko Tsukita ,&nbsp;Yumiko Kutoku ,&nbsp;Yutaka Ohsawa ,&nbsp;Yoshihide Sunada ,&nbsp;Naruhiko Sahara ,&nbsp;Nicholas M. Kanaan ,&nbsp;Makoto Higuchi ,&nbsp;Kohji Mori ,&nbsp;Manabu Ikeda ,&nbsp;Haruhisa Inoue","doi":"10.1016/j.ejcb.2025.151484","DOIUrl":"10.1016/j.ejcb.2025.151484","url":null,"abstract":"<div><div>Frontotemporal Lobar Degeneration (FTLD) is a neurodegenerative disorder that affects the frontal and temporal lobes, which are crucial for regulating personality, behavior, and language. Pathologically, FTLD is characterized by Tau protein accumulation and neuronal death. In our effort to identify disease-modifying treatments, we conducted drug screening using neurons derived from induced pluripotent stem cells (iPSCs) of FTLD-Tau patients. This screening identified gabapentin as an existing drug that suppresses neuronal cell death with suppressed accumulation of Tau oligomers. Treatment with gabapentinoids, including pregabalin and mirogabalin, demonstrated similar neuroprotective effects. These compounds bind to the α2δ subunit of voltage-dependent calcium channels and specifically target the two isoforms α2δ-1 and α2δ-2. To determine which isoform is involved in the neurodegeneration seen in FTLD-Tau, we employed a knockout approach using iPSCs, which revealed that α2δ-2, encoded by CACNA2D2, plays a key role in the degeneration of FTLD-Tau neurons. Moreover, Neural organoids of FTLD-Tau exhibited features indicative of neurodegeneration, and CACNA2D2 knockout reversed a part of the gene expression alterations associated with these neurodegenerative features. These findings suggest that α2δ-2 may be a promising target for disease-modifying therapies in FTLD-Tau.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151484"},"PeriodicalIF":4.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724353","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":"The role of prostanoids in regulatory T cells and their implications in inflammatory diseases and cancers","authors":"Somsak Prasongtanakij ,&nbsp;Kitipong Soontrapa ,&nbsp;Dean Thumkeo","doi":"10.1016/j.ejcb.2025.151482","DOIUrl":"10.1016/j.ejcb.2025.151482","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) play an important role in the immune system through the regulation of immunological self-tolerance and homeostasis. Furthermore, increasing evidence suggests the potential contribution of Tregs beyond immunity in the process of repairing various injured tissues. Tregs are generally characterised by the constitutive expression of forkhead box protein 3 (FOXP3) transcription factor in the nucleus and high expression levels of CD25 and CTLA-4 on the cell surface. To date, a large number of molecules have been identified as key regulators of Treg differentiation and function. Among these molecules are prostanoids, which are multifaceted lipid mediators. Prostanoids are produced from arachidonic acid through the catalytic activity of the enzyme cyclooxygenase and exert their functions through the 9 cognate receptors, DP1‐2, EP1-EP4, FP, IP and TP. We briefly review previous studies on the regulatory mechanism of Tregs and then discuss recent works on the modulatory role of prostanoids.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151482"},"PeriodicalIF":4.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767452","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":"The dual nature of KLHL proteins: From cellular regulators to disease drivers","authors":"Verdiana Di Giulio ,&nbsp;Angelo Canciello ,&nbsp;Erminia Carletti ,&nbsp;Antonella De Luca ,&nbsp;Antonio Giordano ,&nbsp;Andrea Morrione ,&nbsp;Jacopo Berardinelli ,&nbsp;Valentina Russo ,&nbsp;Domenico Solari ,&nbsp;Luigi Maria Cavallo ,&nbsp;Barbara Barboni","doi":"10.1016/j.ejcb.2025.151483","DOIUrl":"10.1016/j.ejcb.2025.151483","url":null,"abstract":"<div><div>The Kelch-like (KLHL) protein family, characterized by its conserved BTB, BACK, and Kelch domains, serves as substrate adaptors for Cullin 3-RING ligases (CRL3), facilitating the ubiquitination and degradation of specific target proteins. Through this mechanism, KLHL proteins regulate numerous physiological processes, including cytoskeletal organization, oxidative stress response, and cell cycle progression. Dysregulation of KLHL proteins—via mutations or abnormal expression—has been implicated in various pathological conditions, including neurodegenerative disorders, cancer, cardiovascular diseases, and hereditary syndromes. This review provides a comprehensive overview of the physiological and pathological roles of KLHL proteins, emphasizing their specific substrates and mechanisms of action. By integrating structural and mechanistic insights with translational research, this review underscores the potential of KLHL proteins as promising therapeutic targets, offering new opportunities to combat a wide spectrum of complex diseases.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151483"},"PeriodicalIF":4.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637269","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":"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}