BMC Molecular and Cell Biology最新文献

{"title":"Chemoradiotherapy-induced Th17/IL-17 signaling correlates with therapeutic tolerance and early recurrence in cervical carcinoma.","authors":"Fanglei Cao, Na Li","doi":"10.1186/s12860-026-00586-8","DOIUrl":"10.1186/s12860-026-00586-8","url":null,"abstract":"<p><p>This study investigates the role of Th17 cells and IL-17 signaling in mediating therapeutic resistance and early recurrence in cervical carcinoma. Th17 cells were generated in vitro, and cervical carcinoma cells were subsequently exposed to cisplatin in the presence of Th17-conditioned media or recombinant IL-17. To elucidate the underlying molecular mechanisms, synthetic siRNAs targeting Akt1 (si-Akt1) and Akt2 (si-Akt2) were employed. Gene expression levels were quantified using ABIVII7 qRT-PCR, and phosphorylation of AKT at Thr308 and Ser473 was assessed. Cervical carcinoma cell lines (HeLa and SW756) were cultured and subjected to siRNA-mediated knockdown of AKT1 and AKT2. Cytotoxicity assays were conducted to evaluate cell viability under various treatment conditions. Cells were stimulated with either standard medium or conditioned medium from in vitro-differentiated Th17 cells. Th17 cell-induced resistance to cisplatin and radiation co-treatment was found to be mediated via the AKT signaling pathway. Moreover, Th17 cells promoted chemoradiotherapy tolerance in cervical cancer cells, with a potential contribution from IL-17 signaling. Although chemoradiotherapy significantly decreased cell viability across all cell lines, preconditioning with recombinant IL-17 notably mitigated this effect, resulting in increased cellular survival. These findings suggest a critical role for Th17 cells in modulating the therapeutic response and recurrence risk in cervical carcinoma through AKT pathway activation.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626682","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":"Telomere-to-telomere characterization of rDNA chromosome in the myxomycete Didymium iridis.","authors":"Arif Khan, Tor Erik Jørgensen, Lars Martin Jakt, Bård Ove Karlsen, Annica Hedberg, Steinar Daae Johansen","doi":"10.1186/s12860-026-00587-7","DOIUrl":"10.1186/s12860-026-00587-7","url":null,"abstract":"<p><strong>Background: </strong>The ribosomal DNA (rDNA) of the myxomycete Didymium iridis is located on a linear, multi-copy, non-Mendelian chromosome. Efforts to determine the complete sequence by short-read sequencing technologies have been prevented by the presence of highly repetitive regions. Here we use high coverage (~10,000 x) long-read Oxford Nanopore Technology to determine the rDNA chromosome sequence in haploid amoebae from telomere-to-telomere.</p><p><strong>Results: </strong>The 20 kb rDNA chromosome, which is present at ~ 132 copies per haploid genome, is capped by regular TTAGGG telomeric repeats at both ends and carries an 11.3 kb pre-rRNA transcription unit coding for the small and large subunit rRNAs. The rRNA genes are further interrupted by autocatalytic group I introns, one of which encodes a homing endonuclease and two catalytic RNA domains with different functions in RNA processing. RNA mapping analyses from amoeba, microcyst, flagellate, and plasmodium stages, based on Illumina short-read sequencing, support the presence of a mature intron homing endonuclease mRNA both in haploid and diploid life stages in D. iridis. The non-transcribed sequence region upstream of the transcription unit contains several direct repeat arrays, including a highly complex upstream promoter region likely to be involved in pre-rRNA transcription regulation. Adjacent to the upstream telomere, a 4.2 kb palindromic region with potential for cruciform structure formation is found. Here, two putative replication origin candidates are located.</p><p><strong>Conclusions: </strong>High coverage Oxford Nanopore Technology sequencing results in excellent resolution of complex sequence repeat feature in the D. iridis rDNA chromosome. The rRNA genes are interrupted by complex group I introns and RNA sequencing supports intron autocatalytic processing in haploid and diploid life stages. This study provides new insights into structural arrangements of nuclear rDNA in eukaryotic microorganisms.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626641","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":"Adult canine pancreatic organoids enable functional analysis of pancreatic epithelial barrier and inflammatory responses.","authors":"Meg Nakazawa, Harry Cridge, Yoko M Ambrosini","doi":"10.1186/s12860-026-00588-6","DOIUrl":"10.1186/s12860-026-00588-6","url":null,"abstract":"<p><p>BACKGROUND: Three-dimensional (3D) organoid cultures from pancreatic tissue are emerging tools for studying pancreatic epithelial development, differentiation, and disease. While models derived from human fetal tissue or adult murine pancreas have provided key insights, their clinical translatability is limited by ethical and species-related differences. The domestic dog offers a valuable intermediate model for translational research, yet pancreatic organoid systems in this species remain underdeveloped. RESULTS: We successfully established long-term organoid cultures from adult canine pancreas and demonstrated their stable ductal phenotype. These organoids exhibited limited but detectable expression of acinar and endocrine markers, indicating partial trilineage potential. We further developed two-dimensional (2D) monolayers from organoids and assessed epithelial barrier integrity using transepithelial electrical resistance (TEER). Monolayers maintained tight junctions and showed media-dependent changes in morphology and KRT19 expression. Peak TEER values exceeded 4000 Ω·cm², confirming robust epithelial barrier function. CONCLUSIONS: This study presents a reproducible protocol for deriving organoids and monolayers from adult canine pancreas, offering a physiologically relevant and ethically accessible model for investigating pancreatic epithelial biology. The combination of 3D and 2D systems enables both lineage characterization and functional assessment, providing a foundation for future applications in regenerative medicine, disease modeling, and comparative translational research. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608045","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":"A role for PaxB in regulating blebbing: experimental insights and theoretical perspectives from Dictyostelium discoideum.","authors":"Zully Santiago, Brian Wey, Sobana Handi Dinuka Sewwandi de Silva, Jessica Reznik, Lamina Siby, Emmanuel Asante-Asamani, Derrick Brazil","doi":"10.1186/s12860-026-00584-w","DOIUrl":"10.1186/s12860-026-00584-w","url":null,"abstract":"<p><p>Eukaryotic cells migrate using pressure-driven blebs or actin polymerization driven pseudopods, with cells preferring to bleb in compressed environments where high protrusion forces are required for movement. In mammals, paxillin is a focal adhesion protein that acts as a scaffold, linking integrins to the actin cytoskeleton and recruiting signaling molecules that regulate adhesion, cytoskeletal remodeling, and migration. Dictyostelium possesses a paxillin ortholog, PaxB, which shares conserved domains with mammalian paxillin and participates in processes such as adhesion, cytokinesis, development, and chemotaxis. However, the role of PaxB in blebbing is not well understood. Our work combines experimental and theoretical methods to elucidate the role of PaxB in blebbing. We use an under-agarose assay to collect data on paxB[Formula: see text] and wild-type cells under low and high compression and observe blebbing characteristics such as area and frequency. Our experimental results point to a role for PaxB in regulating the relative size of blebs in response to increased compression. Using a mathematical model of bleb expansion, we show that decreasing the assembly rate of the cortex during bleb formation leads to relatively larger blebs, thus providing a potential mechanism that replicates the mutant phenotype. Together, our experiments and theory suggest a new role of PaxB in bleb-based chemotaxis.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590051","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":"Chemotactic motion of coronin-null cells with impaired actin turnover.","authors":"Mary Ecke, Jana Prassler, Annette Müller-Taubenberger, Günther Gerisch","doi":"10.1186/s12860-026-00585-9","DOIUrl":"10.1186/s12860-026-00585-9","url":null,"abstract":"<p><p>BACKGROUND: Previous studies have shown that Dictyostelium discoideum cells lacking the actin-regulating protein coronin A have a large hyaline zone at the front of the cell. However, the coronin mutant cells can efficiently navigate in a gradient of chemoattractant by extending rounded protrusions from the hyaline zone. This study examines whether this zone is occupied by actin filaments, as was previously assumed, or if it is free of filamentous actin, as would be the case for typical blebs. RESULTS: The lack of coronin A results in a large hyaline region in the anterior part of mutant cells, from which the endoplasmic reticulum is displaced. This zone is populated with filamentous actin. Despite this broadened front, the coronin-null cells can respond in a gradient of chemoattractant even when they lack actin-based structures such as filopodia or lamellipodia. During re-orientation into a changed direction of the gradient, the mutant cells form rounded protrusions in various directions, of which the one pointing to the direction of the gradient will expand and become the new front. Contact with a substratum is not necessary for a protrusion to be formed in the right direction. These results illustrate the altered but efficient chemotactic responses of cells under conditions of diminished actin filament turnover. CONCLUSIONS: Despite an impaired actin filament turnover, Dictyostelium discoideum cells lacking coronin A respond to a gradient of chemoattractant by extending rounded protrusions from their large hyaline fronts. These protrusions are rich in filamentous actin, and filopodia or lamellipodia are not required. This mode of chemotactic migration is different from a bleb-driven mode described for Dictyostelium and other eukaryotic cells. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520025","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":"Investigating the roles of macrophage age and circulating extracellular vesicles in cytoprotection of hypoxic renal tubular cell stress.","authors":"Dora Livkisa, David J Lundy, Tsung-Lin Lee, Barbara Szomolay, Chia-Te Liao","doi":"10.1186/s12860-026-00583-x","DOIUrl":"10.1186/s12860-026-00583-x","url":null,"abstract":"<p><p>BACKGROUND: Acute kidney injury (AKI) involves complex crosstalk between tubular epithelial cells (TECs) and immune cells. Extracellular vesicles (EVs) and ageing have emerged as modulators of this process. METHODS: We investigated the effects of circulating plasma EVs from young (Y_EVs) and old (O_EVs) mice on hypoxic TEC stress, using bone marrow–derived macrophages (BMDMs) from young or old mice, which were pre-conditioned with EVs. First, direct effects of EVs on TEC viability were assessed following hypoxia/reoxygenation injury. We then examined macrophage responses to hypoxic TEC secretomes with or without EV priming, and tested whether EV-primed BMDM secretomes modulated TEC damage, in terms of viability, cytokine expression, and epithelial–mesenchymal transition (EMT). RESULTS: EVs exerted no direct protective effect on hypoxic TECs, and no significant differences were observed between Y_EVs and O_EVs in any condition. Instead, macrophage donor age was the most significant determinant of outcomes. Conditioned medium from old BMDMs consistently improved TEC viability compared to young BMDMs. In agreement with this, the old mouse BMDM secretome also suppressed hypoxia-induced cytokine expression (Il6, Ccl2) and EMT marker induction (Acta2, Fn1) in hypoxic TECs. EV pre-treatment of BMDMs did not significantly alter these effects in either macrophage group. Thus, BMDM donor age, rather than EV donor age, was the critical driver of cytoprotection and inflammatory modulation in this model. CONCLUSION: Circulating plasma EV age had no significant direct or indirect impacts on TEC viability, inflammatory responses or EMT processes under the tested conditions. This contrasts with prior studies which have suggested broadly rejuvenating effects of young EVs and detrimental effects of old EVs. CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509361","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":"Ciliary p75 neurotrophin receptor (p75NTR) facilitates the enrichment of exogenous amyloid beta (Aβ 1-42) peptide and promotes oxidative stress in human hippocampal astrocytes.","authors":"Ankan Gupta, Karthikeyan Thirugnanam, Zachary Bice, Allison K Lowman, Kevin R Rarick, Peter S LaViolette, Amy Pan, Malgorzata Franczak, Ramani Ramchandran","doi":"10.1186/s12860-026-00581-z","DOIUrl":"10.1186/s12860-026-00581-z","url":null,"abstract":"<p><p>Accumulation of amyloid beta 1–42 (Aβ42) peptide in the extracellular space in the brain is a major observation in Alzheimer’s Disease (AD)-related pathology. Astrocytes are known to play pivotal role in clearing the extracellular aβ peptide from the brain, and the underlying mechanism of Aβ42 peptide clearance remains underappreciated. Like other cell types in the brain, astrocytes have primary cilia, a nonmotile microtubule-based organelle. Aβ42 peptide is reported to affect cilia length or structure in multiple cell types including neurons and inhibit ciliary p75 neurotrophin receptor (p75NTR). To date, the relationship between the extracellular Aβ42 and the astrocytic cilia has not been established. In this work, using primary human hippocampal astrocytes and post-mortem brain specimens obtained from AD patients, we performed molecular, flow cytometry and imaging approaches to investigate the relationship of astrocytic cilia and extracellular Aβ42 peptide. Our data demonstrate that the exogenous Aβ42 peptide treatment in vitro, induces expression of p75NTR in astrocyte cilia in a dose-dependent fashion. We also observed the enrichment of exogenous Aβ42 peptide in the astrocyte cilia and the plasma membrane of astrocytes. In exogenous Aβ42 peptide-treated groups, we observed aberrant proliferation and cell cycle, increased oxidative stress and apoptosis. Interestingly, we observed an enrichment of astrocytic p75NTR expression in the human post-mortem AD-brain. Silencing RNA (siRNA)-mediated knockdown of p75NTR gene significantly minimized the enrichment of exogenous Aβ peptide and the oxidative stress in primary hippocampal astrocytes in vitro. These studies unravel a molecular signaling mechanism that involves Aβ42 peptide-induced p75NTR-mediated oxidative stress that affects overall astrocyte health in AD-associated pathology.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479721","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":"Nutrient and heat stress induce changes to the solubility of predicted prion-like proteins in Dictyostelium discoideum.","authors":"Felicia N Williams, Kanesha Travis, Yaneli Guerra-Hernandez, Erik Soderblom, K Matthew Scaglione","doi":"10.1186/s12860-026-00582-y","DOIUrl":"10.1186/s12860-026-00582-y","url":null,"abstract":"<p><strong>Background: </strong>Dictyostelium discoideum has a unique proteome among sequenced organisms that encodes nearly 10,000 homopolymeric amino acid tracts longer than 10 amino acids long. These repeats are composed of every amino acid except tryptophan with asparagine and glutamine being the most prevalent. Interestingly, asparagine and glutamine-rich regions of proteins are the hallmark of prion-like domains and nearly 25% of the Dictyostelium proteome is predicted to be prion-like in nature.</p><p><strong>Results: </strong>Here we assessed the insoluble proteome upon heat stress or during nutrient stress which induces Dictyostelium development. We found that both heat and nutrient stress induce the accumulation of predicted prion-like proteins in the insoluble fraction; however, the overall amino acid composition of insoluble proteins is different depending on the stress with a greater percentage of predicted prion-like proteins becoming insoluble upon nutrient stress. We further confirmed that endogenous polyglutamine proteins accumulate in the insoluble fraction over the developmental time course and demonstrate that exogenously expressed polyglutamine tracts form puncta and have reduced solubility in a polyglutamine length dependent manner upon nutrient stress. Finally, using a proximity labeling approach, we found that exogenously expressed polyglutamine tracts have enhanced proximity to glutamine-rich proteins.</p><p><strong>Conclusion: </strong>During heat and nutrient stress Dictyostelium have numerous proteins that have decreased solubility. Among these proteins, predicted prion-like proteins are enriched and the presence of a polyglutamine tract is sufficient to cause decreased solubility in a polyglutamine length dependent manner.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442815","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":"Regulation of tRNA expression during the social cycle of the amoeba Dictyostelium discoideum.","authors":"Dulce I Valdivia, Peter F Stadler","doi":"10.1186/s12860-026-00580-0","DOIUrl":"10.1186/s12860-026-00580-0","url":null,"abstract":"<p><p>Transfer RNAs (tRNAs) are the decoders of the protein coding genetic information, as they transfer amino acids into nascent proteins during messenger RNA translation. This pivotal role makes tRNAs a source of translation regulation that can affect protein synthesis. Still, we are beginning to understand the upstream mechanisms regulating tRNA pools themselves. In Dictyostelium discoideum, starvation of a sufficient number of individuals, triggers the development of a coordinated sporulation response denominated the social cycle. By using publicly available transcriptomic, epigenomic, and genomic data, we studied two factors contributing to the regulation of tRNA pools throughout this social cycle. First, the tRNA gene repertoire shows that the compact genome of D. discoideum escapes translational selection as even with a relatively high number of tRNA genes, anticodon and codon frequencies greatly mismatch. This disparity is explained by the overrepresentation of anticodons that can be modified in the wobble position. During the social cycle, the vast majority of tRNA genes lie in nucleosome free regions, indicating that most genes are always contributing to the tRNA pools. However, there is a marked variation in expression levels of the proteins involved in tRNA maturation. This modulation is ultimately mirrored by fine-tuned differential composition of tRNA pools at isodecoder, isoacceptor and isotype levels. Particularly, there is an overall down-regulation in the vegetative to streaming transition. Key elements bypass this down-regulation pattern and taken together, this evidence suggests compensatory mechanisms in tRNA regulation that might rescue translation for the following developmental stages, thus allowing D. discoideum to evolve this remarkable strategy under the pressure of an amino acid scarce environment.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372283","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":"Splicing isoforms associated with TGFβ-induced myofibroblast activation.","authors":"Opeoluwa Alli-Oke, Danny Bergeron, Fiona Kessai, Philippe Thibault, Mathieu Durand, Jean-Philippe Brosseau","doi":"10.1186/s12860-026-00579-7","DOIUrl":"10.1186/s12860-026-00579-7","url":null,"abstract":"<p><p>BACKGROUND: Myofibroblast differentiation is a key process in developmental biology and involved in numerous physiopathology. The gene expression program orchestrating fibroblast to myofibroblast differentiation, as well as its recapitulation by TGFβ stimulation in vitro, is relatively well characterized. Intriguingly, it is known that the splicing isoform EDA+FN1 is a marker and driver of myofibroblast differentiation, but the alternative splicing landscape of myofibroblast is unknown. RESULTS: Here, we performed a high-throughput transcriptomic approach by RNA-Seq in a primary skin fibroblast line and uncover more than 250 splicing isoforms associated with TGFβ-induced myofibroblasts using two different bioinformatic pipelines. This splicing profile highlights a distinct layer of regulation when compared to the global gene expression profile of myofibroblasts. A 5 alternative splicing event (ASE) signature [ACTN1-19 A/19B; COL5A1-64 A/64B; COL6A3 exon 4; FLNA exon 30 and TPM1-6a/6b] was further validated by ddPCR and AS-PCR and retrieved in publicly available RNA-Seq datasets describing other TGFβ-stimulated lung and skin fibroblasts. Surprisingly, TGFβ does not induce an EDA+FN1 splicing shift, although it stimulates global fibronectin expression. CONCLUSIONS: Thus, we conclude that the 5 ASEs signature may be used as putative universal myofibroblast markers and be of functional significance to myofibroblast formation and biology. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364009","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}