Cell and Tissue Research最新文献

{"title":"Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.","authors":"Abdoulaye Diane, Razik Bin Abdul Mu-U-Min, Heba Hussain Al-Siddiqi","doi":"10.1007/s00441-025-03952-8","DOIUrl":"10.1007/s00441-025-03952-8","url":null,"abstract":"<p><p>Impaired insulin secretion contributes to the pathogenesis of type 1 diabetes mellitus through autoimmune destruction of pancreatic β-cells and the pathogenesis of severe forms of type 2 diabetes mellitus through β-cell dedifferentiation and other mechanisms. Replenishment of malfunctioning β-cells via islet transplantation has the potential to induce long-term glycemic control in the body. However, this treatment option cannot widely be implemented in clinical due to healthy islet donor shortage. Emerging β-cell replacement with human-induced pluripotent stem cell (iPSC) provides high remedial therapy hopes. Thus, tremendous progress has been made in developing β-cell differentiation protocols in vitro; however, most of the differentiated iPSC-derived β-cells showed immature phenotypes associated with low efficiency depending on the iPSC lines used, creating a crucial barrier for their clinical implementation. Multiple mechanisms including differences in genetic, cell cycle patterns, and mitochondrial dysfunction underlie the defective differentiation propensity of iPSC into insulin-producing β-cells. Accumulating evidence recently indicated that, following the reprogramming, epigenetic memory inherited from parental cells substantially affects the differentiation capacity of many iPSC lines. Therefore, differences in epigenetic signature are likely to be essential contributing factors influencing the propensity of iPSC differentiation. In this review, we will document the impact of the epigenome on the reprogramming efficacy and differentiation potential of iPSCs and how targeting the epigenetic residual memory could be an additional strategy to improve the differentiation efficiency of existing protocols to generate fully functional hPSC-derived pancreatic β-cells for diabetes therapy and drug screening.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"267-276"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063946","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":"In situ spatial transcriptomic analysis of human skeletal muscle using the Xenium platform.","authors":"Nejc Umek, Marija Meznarič, Žiga Šink, Kaja Blagotinšek Cokan, Uršula Prosenc Zmrzljak, Simon Horvat","doi":"10.1007/s00441-024-03945-z","DOIUrl":"10.1007/s00441-024-03945-z","url":null,"abstract":"<p><p>Traditional transcriptomic studies often overlook the complex heterogeneity of skeletal muscle, as they typically isolate RNA from mixed muscle fibre and cell populations, resulting in an averaged transcriptomic profile that obscures fibre type-specific differences. This study assessed the potential of the recently developed Xenium platform for high-resolution spatial transcriptomic analysis of human skeletal muscle histological sections. Human vastus lateralis muscle samples from two individuals were analysed using the Xenium platform and Human Multi-Tissue and Cancer Panel targeting 377 genes complemented by staining of successive sections for Myosin Heavy Chain isoforms to differentiate between type 1 and type 2 muscle fibres. Manual segmentation of muscle fibres allowed accurate comparisons of transcript densities across fibre types and subcellular regions, overcoming limitations in the platform's automated segmentation. The analysis revealed higher transcript density in type 1 fibres, particularly in nuclear and perinuclear areas, and identified 191 out of 377 genes with differential expression between muscle fibres and perimysium. Genes such as PROX1, S100A1, LGR5, ACTA2, and LPL exhibited higher expression in type 1 fibres, whereas PEBP4, CAVIN1, GATM, and PVALB in type 2 fibres. We demonstrated that the Xenium platform is capable of high-resolution spatial in situ transcriptomic analysis of skeletal muscle histological sections. This study demonstrates that, with manual segmentation, the Xenium platform effectively performs fibre type-specific transcriptomic analysis, providing new insights into skeletal muscle biology.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"291-302"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945143","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":"Extracellular vesicles support increased expansion of mesenchymal stromal cells on fetal membrane-derived decellularized extracellular matrix.","authors":"Aida Shakouri-Motlagh, Andrea J O'Connor, Shaun P Brennecke, Daniel E Heath, Bill Kalionis","doi":"10.1007/s00441-024-03946-y","DOIUrl":"10.1007/s00441-024-03946-y","url":null,"abstract":"<p><p>Decidual mesenchymal stromal cells (DMSC) were the source of extracellular vesicles (DMSC_EV). The xCELLigence real-time cell growth assay revealed increasing concentrations of EVs decreased DMSC attachment in the early growth phase but stimulated DMSC proliferation at day 7 when grown on tissue culture plastic (TCP). DMSC attachment and proliferation varied depending on the growth surface and DMSC_EV supplementation. DMSC attachment increased on decellularized and solubilized amniotic (s-dAM) whether or not EVs were added. Only Matrigel substrate increased DMSC attachment with added EVs. The addition of EVs increased DMSC proliferation only on the s-dAM substrate. DMSCs were more motile on s-dAM and decellularized and solubilized chorionic (s-dCM) membranes following EV addition. The osteogenic potential of DMSCs was improved on s-dAM substrates when supplanted with EVs. Finally, the levels of reactive oxygen species in DMSCs varied depending on the substrate but not on added EVs. We show that the addition of in vitro EVs isolated from the source being expanded (i.e., DMSCs) and the presence of ECM improve DMSC behaviours during ex vivo expansion. The inclusion of two key components of the MSC niche, EVs and ECM, benefitted the ex vivo expansion of MSCs. Added in vitro EVs increased the proliferation of DMSCs when grown on s-dAM but not on s-dCM, whereas they improved DMSC mobility on both surfaces. Testing different ECMs could be used to promote specific desired characteristics of DMSCs, and different combinations of EVs and ECM may enhance desirable MSC characteristics for specific therapeutic settings.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"323-336"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881381","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":"Identification of glutamate-related disease-dependent alterations in subventricular NSCs of the 3xTg Alzheimer's disease model, could they be involved in attempting damage repair?","authors":"Giorgia Cerqueni, Valentina Terenzi, Alessandra Preziuso, Tiziano Serfilippi, Silvia Piccirillo, Mariangela Di Vincenzo, Patrizia Ambrogini, Salvatore Amoroso, Monia Orciani, Vincenzo Lariccia, Simona Magi","doi":"10.1007/s00441-025-03954-6","DOIUrl":"https://doi.org/10.1007/s00441-025-03954-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by several factors, such as impaired glutamate neurotransmission affecting crucial functions. Neural stem cells (NSCs) are present in the adult brains of all mammalian species and contribute to the continuous generation of neural cells throughout life. The disruption of glutamate levels during the development of AD could impact NSCs' functionality, influencing their response to the microenvironment. In this work, we isolated adult neural stem cells from both triple transgenic (3xTg)-AD mice and age-matched wild type (WT) mice in order to gather information on any differences between them, particularly concerning the potential mechanisms involved in the internalisation of glutamate and its utilisation for energy production. The 3xTg model offers the ability to recapitulate human pathology with both plaque and tangle hallmarks that are involved in the process of glutamate release. In vitro culture 3xTg NSCs showed a slight morphological difference compared to WT cells and a massive reduction of proliferation and viability. Furthermore, 3xTg NSCs displayed an increase in the expression of glutamate transporters and glutamine synthetase, while glutamate dehydrogenase did not show any reduction, which is typical in AD brains. Data obtained from this basic research study suggest a possible involvement of glutamate in the cellular energy balance, indicating an attempted response of NSCs to the cytotoxic microenvironment in the early stage of AD pathology. This finding is of great interest, as it corroborates the hypothesis that targeting the glutamatergic system could be an extremely promising strategy for new therapeutics in AD.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440032","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":"A brief history of insect neuropeptide and peptide hormone research.","authors":"Dick R Nässel","doi":"10.1007/s00441-024-03936-0","DOIUrl":"10.1007/s00441-024-03936-0","url":null,"abstract":"<p><p>This review briefly summarizes 50 years of research on insect neuropeptide and peptide hormone (collectively abbreviated NPH) signaling, starting with the sequencing of proctolin in 1975. The first 25 years, before the sequencing of the Drosophila genome, were characterized by efforts to identify novel NPHs by biochemical means, mapping of their distribution in neurons, neurosecretory cells, and endocrine cells of the intestine. Functional studies of NPHs were predominantly dealing with hormonal aspects of peptides and many employed ex vivo assays. With the annotation of the Drosophila genome, and more specifically of the NPHs and their receptors in Drosophila and other insects, a new era followed. This started with matching of NPH ligands to orphan receptors, and studies to localize NPHs with improved detection methods. Important advances were made with introduction of a rich repertoire of innovative molecular genetic approaches to localize and interfere with expression or function of NPHs and their receptors. These methods enabled cell- or circuit-specific interference with NPH signaling for in vivo assays to determine roles in behavior and physiology, imaging of neuronal activity, and analysis of connectivity in peptidergic circuits. Recent years have seen a dramatic increase in reports on the multiple functions of NPHs in development, physiology and behavior. Importantly, we can now appreciate the pleiotropic functions of NPHs, as well as the functional peptidergic \"networks\" where state dependent NPH signaling ensures behavioral plasticity and systemic homeostasis.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"129-159"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799500","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":"Development of a 3D in vitro model to study corpus luteum of felids based on luteinized cells from antral follicles.","authors":"Michał M Hryciuk, Filip Schröter, Svenja Claaßen, Christine Aurich, Jella Wauters, Celina Haße, Beate C Braun","doi":"10.1007/s00441-024-03937-z","DOIUrl":"10.1007/s00441-024-03937-z","url":null,"abstract":"<p><p>The study aimed to establish a long-term 3D cell culture model using luteinized follicular cells to investigate the functionality and life cycle of the CL in felids. A mixture of cell types from antral follicles was luteinized in vitro and cultured for up to 23 days. The method, initially applied to the domestic cat, was later extended to Persian and Clouded leopards. Antral follicles were isolated and digested with enzymes; then, the cells were subjected to culture. Experimental subsets were treated with/without 1 µg/mL cloprostenol to validate the cell culture model's suitability for functional studies. In domestic cat samples, microscopic evaluation indicated luteinization, which was confirmed by increased progestagen concentrations and IHC staining for HSD3B and CYP11A1. The gene expression of selected steroidogenic factors (HSD3B1, STAR, CYP11A1) and hormone receptors (LHCGR, PTGFR, PRLR) significantly increased, while CYP17A1 expression decreased. Cloprostenol treatment resulted in reduction of steroidogenic activity, proving its suitability for functional studies. Persian and Clouded leopards' cell cultures exhibited similar patterns in progestagen secretion and gene expression, compared to domestic cats. This model, with its defined luteinization, as well as high and stable progestagen production, allows future investigation of factors regulating CL life cycle and function.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"211-229"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853124","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":"Foxa1 disruption enhances human cell integration in human-mouse interspecies chimeras.","authors":"Li-Na Wang, Jun-Shuang Jia, Xing-Long Yang, Yue-Ting Wen, Jing-Xian Liu, Deng-Ke Li, Xing-Rui Chen, Jia-Hong Wang, Ji-Ke Li, Zhong-Xi Huang, Kai-Tai Yao","doi":"10.1007/s00441-024-03941-3","DOIUrl":"10.1007/s00441-024-03941-3","url":null,"abstract":"<p><p>Blastocyst complementation can potentially generate a rodent model with humanized nasopharyngeal epithelium (NE) that supports sustained Epstein-Barr virus (EBV) infection, enabling comprehensive studies of EBV biology in nasopharyngeal carcinoma. However, during this process, the specific gene knockouts required to establish a developmental niche for NE remain unclear. We performed bioinformatics analyses and generated Foxa1 mutant mice to confirm that Foxa1 disruption could potentially create a developmental niche for NE. Subsequently, MYD88-inactivated human pluripotent stem cells (hPSCs) were constructed and complemented with Foxa1-deficient mouse blastocysts, with Nosip-deficient mouse blastocysts as a control. The chimerism of human cells in mouse embryos was evaluated from E8.5 to E12.5 using genomic DNA PCR and immunohistochemistry. Our bioinformatics analysis indicated that the expression patterns of Foxa1 in E8.5 to E16.5 mouse embryos underscore its critical role in NE development. The generated mice with Foxa1 disordered region mutations displayed morphological abnormality in NE, suggesting Foxa1-knockouts could potentially establish a developmental niche for NE. In chimeric assays, human cells integrated into 80.00% of Foxa1-deficient embryos, compared with the 4.17% in controls. Immunohistochemistry results revealed robust proliferation of human cells in Foxa1-deficient mouse embryos. However, chimeras from Foxa1-deficient mouse embryos did not survive beyond E10.5, hindering the evaluation of human cell integration in mouse NE. Foxa1 disruption in mouse embryos significantly enhances the integration of human cells in human-mouse interspecies chimeras, thereby facilitating the generation of endoderm-derived organs through blastocyst complementation. Overcoming chimeras' embryonic lethality is crucial for successfully generating humanized NE in Foxa1-deficient mouse embryos.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"231-245"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871462","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":"Enhancer Enh483 regulates myoblast proliferation and differentiation of buffalo myoblasts by targeting FAXC.","authors":"Yaling Chen, Jiahui Zhao, Cuiwei Zhong, Yujin Kang, Zhaocheng Xiong, Jieping Huang, Zhipeng Li, Qingyou Liu, Deshun Shi, Xinxin Li, Jian Wang, Hui Li","doi":"10.1007/s00441-024-03944-0","DOIUrl":"10.1007/s00441-024-03944-0","url":null,"abstract":"<p><p>A detailed understanding of the precise regulatory mechanisms governing buffalo skeletal muscle is crucial for improving meat quality and yield. Proper skeletal muscle fate decisions necessitate the accurate regulation of key enhancers. This study screened nine potential enhancers linked to muscle development by analysing ATAC-seq data from buffalo myoblasts during the proliferative and differentiative phases. The enhancer activity of these candidates was confirmed in buffalo myoblasts, C2C12, and human skeletal muscle myoblasts using a dual-luciferase reporter system. The CRISPRi system and RT-qPCR were used to test the effects of 9 candidate enhancers on buffalo myoblasts. The active enhancer, Enh483, was selected based on its significant impact. Upon successful inhibition of Enh483 using CRISPRi, decreases in the expression of buffalo myogenic proliferation marker genes (PCNA, CyclinD1, and CDK2) were observed via RT-qPCR and Western blot. Subsequent proliferation assays using CCK-8 and EdU confirmed the promotive effect of Enh483 on buffalo myogenic cell proliferation. Following a 5-day differentiation induction period, changes in the expression of differentiation marker genes (MyoD1, MyoG, and MyHC) were analysed using RT-qPCR and Western blot. Additionally, fused myotube numbers were quantified, and the impact of Enh483 on buffalo myogenic cell differentiation was assessed through immunofluorescence. Our findings indicate that Enh483 facilitates buffalo myogenic cell differentiation. Further interaction analysis utilising 3C-PCR revealed a direct association between Enh483 and the FAXC promoter. In summary, the results from this study lay a foundational framework for deciphering the intricate regulatory mechanisms underpinning buffalo muscle development.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"161-171"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834056","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":"Organization of the stalk system on electrocytes in mormyrid weakly electric fish Campylomormyrus compressirostris.","authors":"Otto Baumann, Feng Cheng, Frank Kirschbaum, Ralph Tiedemann","doi":"10.1007/s00441-024-03938-y","DOIUrl":"10.1007/s00441-024-03938-y","url":null,"abstract":"<p><p>The adult electric organ in weakly electric mormyrid fish consists of action-potential-generating electrocytes, structurally and functionally modified skeletal muscle cells. The electrocytes have a disc-shaped portion and, on one of its sides, numerous thin processes, termed stalklets. These unite to stalks leading to a single main stalk that carries the innervation site. Here, we describe the 3-dimensional layout of the stalklet/stalk system in adult Campylomormyrus compressirostris by differential interference contrast microscopy and confocal fluorescence microscopy. Using antibodies against Na⁺/K⁺-ATPase α-subunit and plasma membrane Ca²⁺-ATPase, we show that these ion pumps are differentially distributed over the stalklet/stalk system, with plasma membrane Ca²⁺-ATPase being enriched on the stalklet membrane. Stalklets are distributed and organized in a quite uniform pattern on the posterior face of the electrocyte disc and fuse to terminal stalks. The latter then unite in a mostly dichotomic mode to stalks of increasing thickness, with the main stalk measuring about 100 µm in diameter. We further analyse the structural organization of stalklets and stalks, with a characteristic cytoskeletal system of bundled actin filaments in the centre and nuclei in subsurface position. These results suggest that the stalklet/stalk system is adapted in its structural layout to generate an action potential highly synchronized over the entire disc-portion of the electrocyte, accounting for the short electric organ discharge in this species. Our results suggest that actin-related proteins overexpressed in electrocytes, as shown previously by transcriptome analysis, may be involved in the organization of the unique F-actin system in stalklets and stalks.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"193-209"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863059","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":"TNBS colitis induces architectural changes and alpha-synuclein overexpression in mouse distal colon: A morphological study.","authors":"Arianna Casini, Giorgio Vivacqua, Ludovica Ceci, Stefano Leone, Rosa Vaccaro, Marco Tagliafierro, Filippo Maria Bassi, Sara Vitale, Emanuele Bocci, Luigi Pannarale, Simone Carotti, Antonio Franchitto, Patrizia Mancini, Roberta Sferra, Antonella Vetuschi, Giovanni Latella, Paolo Onori, Eugenio Gaudio, Romina Mancinelli","doi":"10.1007/s00441-024-03932-4","DOIUrl":"10.1007/s00441-024-03932-4","url":null,"abstract":"<p><p>Alpha-synuclein (α-syn) is widely expressed in presynaptic neuron terminals, and its structural alterations play an important role in the pathogenesis of Parkinson's disease (PD). Aggregated α-syn has been found in brain, in the peripheral nerves of the enteric nervous system (ENS) and in the intestinal neuroendocrine cells during synucleinopathies and inflammatory bowel disorders. In the present study, we evaluated the histomorphological features of murine colon with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a common model of colitis. Thereafter, we investigated the expression of α-syn, Toll-like receptor 4 (TLR4), choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), and calcitonin-like receptor (CALCR). Finally, we investigated the presence of phosphorylated α-syn (pS129 α-syn) aggregates and their relationship with inflammatory cells. Colon from TNBS mice showed an increase in inflammatory cells infiltrate and significative changes in the architecture of the intestinal mucosa. α-Syn expression was significantly higher in inflamed colon. VIP was increased in both the mucosa and muscularis externa of TNBS mice, while TH, CGRP, and CALCR were significantly reduced in TNBS mice. Amyloid aggregates of pS129 α-syn were detectable in the ENS, as in the macrophages around the glands of the mucosa correlating with the markers of inflammation. This study describes - for the first time - the altered expression of α-syn and the occurrence of amyloid α-syn aggregates in the inflammatory cells under colitis, supporting the critical role of bowel inflammation in synucleinopathies and the involvement of α-syn in IBD.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":" ","pages":"247-265"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799434","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}