Philipp Berger , Lisa Wilming , Ricarda Jürgens , Yevheniia Minchuk , Sophia Leußink , Shrey Gandhi , Carolin Walter , Sophie-Marie Wind , Dominik Heider , Lukas Lamparter , Milos Galic , Monika Stoll , Selina K. Jorch , Johannes Roth , Judith Austermann , Olesja Fehler
{"title":"PSTPIP1 and pyrin, two key regulators of macrophage differentiation","authors":"Philipp Berger , Lisa Wilming , Ricarda Jürgens , Yevheniia Minchuk , Sophia Leußink , Shrey Gandhi , Carolin Walter , Sophie-Marie Wind , Dominik Heider , Lukas Lamparter , Milos Galic , Monika Stoll , Selina K. Jorch , Johannes Roth , Judith Austermann , Olesja Fehler","doi":"10.1016/j.ejcb.2025.151518","DOIUrl":"10.1016/j.ejcb.2025.151518","url":null,"abstract":"<div><h3>Background</h3><div>Monocytes develop from hematopoietic stem cells; migrate into the tissue, where they undergo a stimulation-dependent and tissue specific differentiation into macrophages imprinting specific inflammatory functions. The development of inflammatory functions during differentiation of progenitor cells into macrophages remained incompletely understood.</div></div><div><h3>Objective</h3><div>We intended to identify regulatory factors driving monocyte/macrophage differentiation.</div></div><div><h3>Methods</h3><div>A Genome-wide CRISPR/Cas9 knockout screen (GeCKO) in ER-HoxB8 macrophages was used to identify key drivers of macrophage differentiation which were verified in independent knock-out and knock-in cells. Immunophenotyping was studied by FACS, morphology and migration by fluorescence microscopy, the inflammatory response by ELISA. Transcriptomic data were obtained by next generation mRNA sequencing and validated by quantitative polymerase chain reaction and immunoblotting.</div></div><div><h3>Results</h3><div>Genome-wide CRISPR/Cas9 knockout screen identified the cytosolic cytoskeleton-associated adaptor molecule PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1) as a regulatory factor of macrophage differentiation. Interestingly, mutations in PSTPIP1 cause autoinflammatory disorders (PAPA syndrome). Deletion of PSTPIP1 resulted in hampered differentiation, decreased inflammatory response, changed morphology, altered cell adhesion and migration properties. PSTPIP1 is a regulator of Pyrin inflammasome activity which drives autoinflammation in familial Mediterranean fever (FMF). Deletion of Pyrin also resulted in a strong alteration of cellular dynamics in macrophages.</div></div><div><h3>Conclusion</h3><div>PSTPIP1 and Pyrin are crucial factors in macrophage differentiation. Their deletion or mutation resulted in a hampered differentiation of macrophages resulting in strong morphological alterations and impacting phagocyte key functions as adhesion and migration. Impaired differentiation of macrophages may represent a significant factor in the pathophysiology of autoinflammatory diseases like FMF and PAPA.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151518"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiwoo Yeom , Sanghoon Lee , Young Ho Ko , Eunmi Hong , Jin Hae Kim , Pierre A. Coulombe , Chang-Hun Lee
{"title":"Structure and function of the keratin 17 tail domain associated with keratin intermediate filament organization","authors":"Jiwoo Yeom , Sanghoon Lee , Young Ho Ko , Eunmi Hong , Jin Hae Kim , Pierre A. Coulombe , Chang-Hun Lee","doi":"10.1016/j.ejcb.2025.151519","DOIUrl":"10.1016/j.ejcb.2025.151519","url":null,"abstract":"<div><div>Keratins are the largest subgroup of intermediate filament proteins, forming 10-nm filaments from type I/II heterodimers, and occur primarily in epithelial cells. Keratin 6 (K6; type II) and Keratin 17 (K17; type I) show a complex expression pattern that includes induction following stress and in several diseases, including carcinomas. K17 is being used as a biomarker for several types of cancer. K6 and K17 sequences are respectively highly homologous to K5 and K14, which are expressed in the progenitor compartment of epidermis and related epithelia. The mechanical support roles of the K6/K17 and K5/K14 pairing require 10 nm filament assembly and the subsequent lateral association of these filaments to form thicker bundles. Previous studies showed that the non-helical tail domain of K14 is dispensable for 10 nm filament assembly but essential to the bundling of K5/K14 filaments. Whether the K6/K17 pairing undergoes bundling, and whether the tail domain of K17 plays a role, is unknown. Here, we use sedimentation assays and electron microscopy to show that, when paired with K6, tailless K17 forms filaments that do not readily bundle. Nuclear magnetic resonance analysis revealed that the isolated K17 tail domain is an intrinsically disordered region (IDR). Follow-up studies with mutant K17 tail constructs suggest that IDR-like tail domains of keratins can form a curved local structure required for bundling and interact dynamically with other regions of keratin filaments in a flexible and heterogeneous manner.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151519"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sterile inflammation in laminopathies","authors":"Rafael Cancado de Faria, Susana Gonzalo","doi":"10.1016/j.ejcb.2025.151512","DOIUrl":"10.1016/j.ejcb.2025.151512","url":null,"abstract":"<div><div>Sterile inflammation, an immune response triggered in the absence of pathogens, plays a key role in various chronic diseases, including aging-related disorders, cancer, and autoimmune conditions. This process is driven by damage-associated molecular patterns, such as self-DNA in the cytosol, which activate innate immune pathways and contribute to persistent inflammation. Chronic activation of these pathways exacerbates tissue damage and accelerates disease progression. Recent studies have connected sterile inflammation to laminopathies, a group of genetic disorders caused by mutations in the <em>LMNA</em> gene, which encodes nuclear intermediate filament proteins essential for nuclear structure and function. In this review we discuss the molecular mechanisms underlying sterile inflammation in laminopathies, emphasizing self-DNA sensing, inflammatory signaling cascade activation, and their pathological consequences. Additionally, we explore potential therapeutic strategies aimed at modulating inflammation and improving disease outcomes. Understanding these interactions may provide new avenues for targeting inflammation in laminopathies and related conditions.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151512"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Lozano-Prieto , Inmaculada Jorge , Emilio Camafeita , Cristina A. Devesa , Rafael Barrero-Rodríguez , Enrique Calvo , Andrea Laguillo-Gómez , Clara Pertusa , Noa B. Martin-Cofreces , Jesús Vázquez , Francisco Sánchez-Madrid
{"title":"Deciphering the landscape of post-translational modifications in the centrosome upon T cell activation","authors":"Marta Lozano-Prieto , Inmaculada Jorge , Emilio Camafeita , Cristina A. Devesa , Rafael Barrero-Rodríguez , Enrique Calvo , Andrea Laguillo-Gómez , Clara Pertusa , Noa B. Martin-Cofreces , Jesús Vázquez , Francisco Sánchez-Madrid","doi":"10.1016/j.ejcb.2025.151521","DOIUrl":"10.1016/j.ejcb.2025.151521","url":null,"abstract":"<div><div>The shift from quiescent to effector T cells (TC) is controlled at the translational level. Post-translational modifications (PTMs) are key factors in the diversification of protein function. Advancements in mass spectrometry-based proteomics enable proteome-wide, hypothesis-free quantitative PTM analysis. Current research highlights the centrosome role in TC activation. Here the diversity of PTMs in the TC centrosome is studied by analyzing centrosome-enriched fractions from human resting and activated T lymphoblasts. Our results show that oxidative modifications predominate in this organelle, with tryptophan as the most frequently oxidized residue. These PTMs are enriched in proteins involved in translation, vesicular trafficking, cytoskeleton organization, among others. We also demonstrate the existence of PTM changes on specific protein regions during TC activation in Myh9 (hyperoxidized), and Gzma (hypoxidized). These hyper- or hypoxidized proteins display distinct functional distributions. Our study provides the first comprehensive PTM mapping of the TC centrosome, underscoring the PTM regulatory role in TC activation.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151521"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisabeth Gludovacz , Grace Wen , Matthias Weiss-Tessbach , Felix Kosta , Gerald Klanert , Mara Heckmann , Anna-Lena Hoebler , Warren L. Lee , Nicole Borth , Bernd Jilma , Thomas Boehm
{"title":"Human diamine oxidase undergoes transcytosis and colocalizes with the plasma membrane monoamine transporter indicating intracellular histamine degradation","authors":"Elisabeth Gludovacz , Grace Wen , Matthias Weiss-Tessbach , Felix Kosta , Gerald Klanert , Mara Heckmann , Anna-Lena Hoebler , Warren L. Lee , Nicole Borth , Bernd Jilma , Thomas Boehm","doi":"10.1016/j.ejcb.2025.151520","DOIUrl":"10.1016/j.ejcb.2025.151520","url":null,"abstract":"<div><div>Secreted human diamine oxidase (hDAO) is the only enzyme capable of extracellular histamine inactivation. Histamine is the key mediator released at high concentrations from activated mast cells causing various unpleasant to life-threatening symptoms. Recombinant hDAO is internalized into various cell types. However, rhDAO-containing intracellular vesicles do not colocalize with the lysosomes indicating that rhDAO is unlikely targeted for direct degradation. After internalization rhDAO was rapidly exocytosed without loss of enzymatic activity and re-internalized. Total internal reflection fluorescence microscopy revealed that rhDAO undergoes transcytosis in endothelial cells. The number of transcytosis events was dose-dependent and saturable indicating a specific, receptor-mediated uptake mechanism. Addition of unlabeled DAO, heparin and heparin-binding motif mutated DAO significantly reduced the number of transcytosis events. After intravenous injection of rhDAO into mice it was detected in vesicles not only within but also below the endothelial cell layer of the thoracic aorta. Localization of hDAO within extracellular vesicles was not detected in biological fluids. In various cell types intracellular vesicular rhDAO colocalized with plasma membrane monoamine transporter (PMAT), but not with the organic cationic transporters 1–3. Histamine is described to be a substrate for all four transporters. Cytoplasmic intravesicular localization of DAO has been detected for many decades but no definite physiological function could be assigned. Newly discovered transcytosis might transport DAO into the interstitial fluid compartment with widespread tissue distribution, especially during pregnancy. Vesicular colocalization of DAO with the histamine transporter PMAT indicates intracellular histamine degradation within these poorly characterized vesicles.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151520"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vimentin in the tumor microenvironment: orchestrating invasion, immunity, and metabolism","authors":"Sepideh Parvanian , John E. Eriksson","doi":"10.1016/j.ejcb.2025.151523","DOIUrl":"10.1016/j.ejcb.2025.151523","url":null,"abstract":"<div><div>Vimentin, a type III intermediate filament protein, has gained recognition as a multifunctional regulator within the tumor microenvironment (TME). While traditionally considered a hallmark of epithelial-to-mesenchymal transition (EMT), vimentin is increasingly understood as a structural and signaling hub essential for the functional complexity of mesoderm-derived and EMT-transitioned cells. It bridges cytoskeletal architecture with key signaling networks, linking cellular plasticity to mechanotransduction, immune modulation, and metabolic regulation. This unique versatility underlies vimentin’s essential role in supporting the migratory, remodeling, and adaptive behaviors required in contexts such as wound healing, inflammation, and tissue remodeling—capabilities that cancer cells have co-opted to their advantage. Indeed, vimentin’s pervasive expression across aggressive cancers reflects its ability to scaffold and coordinate the cytoskeletal and signaling rewiring needed for malignancy. This review provides an integrated overview of vimentin’s diverse roles in the TME, emphasizing its contributions to tumor invasiveness, immune regulation, and metabolic adaptation. We conclude by discussing how these insights may inform the development of vimentin-centered strategies to improve therapeutic outcomes in cancer.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151523"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Salvador-Mira , Paula Gimenez-Moya , Alba Manso-Aznar , Ester Sánchez-Córdoba , Manuel A. Sevilla-Diez , Veronica Chico , Ivan Nombela , Sara Puente-Marin , Nerea Roher , Luis Perez , Tanja Dučić , Núria Benseny-Cases , Ana Joaquina Perez-Berna , Maria del Mar Ortega-Villaizan
{"title":"Corrigendum to “Viral vaccines promote endoplasmic reticulum stress-induced unfolding protein response in teleost erythrocytes” [Eur. J. Cell Biol. 104 (2025) 151490]","authors":"Maria Salvador-Mira , Paula Gimenez-Moya , Alba Manso-Aznar , Ester Sánchez-Córdoba , Manuel A. Sevilla-Diez , Veronica Chico , Ivan Nombela , Sara Puente-Marin , Nerea Roher , Luis Perez , Tanja Dučić , Núria Benseny-Cases , Ana Joaquina Perez-Berna , Maria del Mar Ortega-Villaizan","doi":"10.1016/j.ejcb.2025.151510","DOIUrl":"10.1016/j.ejcb.2025.151510","url":null,"abstract":"","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151510"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole Schwarz , Rudolf E. Leube , Stefan Düsterhöft
{"title":"Comprehensive in silico analyses of keratin heterodimerisation","authors":"Nicole Schwarz , Rudolf E. Leube , Stefan Düsterhöft","doi":"10.1016/j.ejcb.2025.151513","DOIUrl":"10.1016/j.ejcb.2025.151513","url":null,"abstract":"<div><div>Keratins are the largest and most diverse group of intermediate filament proteins, providing structural integrity and mechanical strength to epithelial cells. Although their assembly as heterodimers is well established, the specific pairing preferences and molecular basis of keratin dimerisation remain largely unknown. Here, we employ a high-throughput computational pipeline that integrates AlphaFold Multimer (AFM) modelling, VoroIF-GNN interaction interface quality assessment, interaction energy calculations and structural comparisons with experimentally solved structures to systematically investigate keratin heterodimerisation and to provide a guideline for further analysis of intermediate filament assembly. To validate our in silico approach, we include the well-studied vimentin homodimer as a reference. The predicted vimentin homodimer shows strong agreement with available experimental data, supporting the accuracy of our modelling pipeline. Our results show that keratin heterodimers generally have lower interaction energies, indicating more favourable interactions, than their homodimer counterparts, and exhibit structural configurations that closely resemble known intermediate filament structures. Comparative analyses of different keratin pairs also reveal the importance of the coil 1 region for dimer stability. Furthermore, co-expression of keratin pairings is demonstrated by analysis of spatial transcriptomics data in skin under physiological and pathological conditions. Collectively, these findings highlight structural principles underlying canonical keratin heterodimerisation and establish a robust computational workflow for elucidating alternative keratin dimerisations.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151513"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Rocha , Jonas Petsch , Dorothea Schultheis , Michaela M. Zrelski , Petra Fichtinger , Inga Koneczny , Samuel Meier-Menches , Gerhard Wiche , Rolf Schröder , Lilli Winter
{"title":"Consequences of plectin ablation on the various intermediate filament systems in skeletal muscle","authors":"Marta Rocha , Jonas Petsch , Dorothea Schultheis , Michaela M. Zrelski , Petra Fichtinger , Inga Koneczny , Samuel Meier-Menches , Gerhard Wiche , Rolf Schröder , Lilli Winter","doi":"10.1016/j.ejcb.2025.151522","DOIUrl":"10.1016/j.ejcb.2025.151522","url":null,"abstract":"<div><div>Plectin, a highly versatile and multifunctional cytolinker, acts as a central connector of the intermediate filament (IF) and other cytoskeletal systems. In skeletal muscle, plectin orchestrates and anchors the extrasarcomeric desmin filament network to sites of strategic importance and thereby substantially contributes to its fundamental biomechanical properties. Lack of plectin in skeletal muscle leads to a faulty organization of the desmin IFs, thereby inflicting a reduced mechanical stress tolerance and a progressive myopathic process. Accordingly, the morphological hallmark of the skeletal muscle pathology in most plectinopathies, including epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is the accumulation of desmin-positive protein aggregates. To address the consequences of plectin-deficiency on other types of IFs, RNA and protein expression as well as localization of various IF subtypes was evaluated in muscle tissue from wild-type and muscle-specific conditional plectin knockout (MCK-Cre/cKO) mice. Notably, vimentin and syncoilin, as well as several other IF subtypes, were significantly upregulated in MCK-Cre/cKO muscles and accumulated in subsarcolemmal and sarcoplasmic areas. In plectin-deficient mouse myoblasts, increased expression levels of vimentin were accompanied by the formation of thickened IF bundles. Primary human myoblasts, treated with the plectin inhibitor plecstatin-1, displayed increased bundling of desmin and vimentin, thus supporting the notion of drastic structural and organizational changes in the network. Finally, we were able to demonstrate the presence of vimentin-positive protein aggregates in skeletal muscle specimens from EBS-MD patients. Together, these data indicate that the depletion of plectin in muscle unequivocally affected the expression and localization of various types of IFs.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151522"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Petra Majerova , Krutika Khiratkar , Michaela Skrabanova , Dominika Olesova , Lubica Fialova , Kevin James , Jozef Vegh , Juraj Piestansky , Andrej Kovac
{"title":"A physiologically relevant blood–cerebrospinal fluid barrier model to study the permeability of neurodegenerative biomarkers","authors":"Petra Majerova , Krutika Khiratkar , Michaela Skrabanova , Dominika Olesova , Lubica Fialova , Kevin James , Jozef Vegh , Juraj Piestansky , Andrej Kovac","doi":"10.1016/j.ejcb.2025.151517","DOIUrl":"10.1016/j.ejcb.2025.151517","url":null,"abstract":"<div><div>The blood–cerebrospinal fluid barrier (BCSFB) is formed by the choroid plexus and represents the interface between the blood and cerebrospinal fluid (CSF). Several in vitro models have been developed to establish an active cellular barrier and to study the functional and molecular properties of the BCSFB. These models are suitable for simulating disease processes and evaluating drug permeability into brain tissue. Here we have established and optimized a protocol for the high-yield isolation of primary epithelial cells from rat choroid plexus. The addition of cytosine arabinoside suppressed the growth of contaminating cells (fibroblasts and astrocytes), and epithelial culture was grown into a confluent impermeable monolayer within 5–6 days after seeding. To characterize functional and structural properties of our BCSFB model, we employed immunocytochemical and biochemical techniques. Using this model, we assessed the permeability of small molecules as well as proteins associated with neurodegenerative disorders, including tau protein and neurofilament light chain (NfL). The cells were able to secrete cerebrospinal fluid (CSF) actively and the epithelial secretome was enriched in growth factors, cell-matrix proteins, proteases, carrier proteins, and inflammation-related proteins. The novelty of our model lies in its ability to mimic the structural and functional characteristics of the BCSFB while also expressing transporters that are important for pharmaceutical research. The model is suitable for in vitro investigations of the BCSFB, preclinical drug discovery, and for studying the mechanisms by which CNS biomarkers cross from the CSF to the blood during disease.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 4","pages":"Article 151517"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145106449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}