BMC Biology最新文献

{"title":"Abl kinase activation promotes axon initial segment disassembly and protein sorting defects in Alzheimer's disease.","authors":"Nicolás Stuardo, Álvaro Cáceres-Quezada, Diego Guzmán, Cristian M Lamaizon, Nancy Leal R, Anthony J Koleske, Alejandra Álvarez R","doi":"10.1186/s12915-026-02624-5","DOIUrl":"10.1186/s12915-026-02624-5","url":null,"abstract":"<p><strong>Background: </strong>Axon initial segment (AIS) dysfunction disrupts neuronal compartmentalization, which leads to pathological processes like Tau missorting in Alzheimer's disease (AD). However, the molecular mechanisms that destabilize the AIS scaffold are incompletely understood. Our group has previously shown that the Abl1 non-receptor tyrosine kinase is aberrantly activated in AD mouse models and promotes dendritic spine collapse, Tau hyperphosphorylation, and neuronal apoptosis. Given the important role of Abl1 in AD and its emerging significance in Tau pathology, we examined how it contributes to AIS collapse.</p><p><strong>Results: </strong>We find that activation of Abl1 by amyloid-β fibrils promotes AIS disruption, as determined by the loss of clustered AnkG in the proximal axon, and that this can be prevented by pharmacological inhibition of Abl kinases. Cytosolic extraction experiments show that active Abl1 associates to the AIS scaffold, and this association increases in response to amyloid-β fibril treatment. Furthermore, using expansion microscopy, we show that Abl1 localizes to the AIS in dissociated hippocampal cultures and in mouse brain slices. We find a decrease in AIS actin patches, key for maintenance of neuronal compartmentalization, following Abl kinase activation. Finally, we show that Abl1 activation promotes missorting of somatodendritic Rab11 into the axon and the axonal protein Tau into the somatodendritic compartment, indicating a bidirectional failure in AIS barrier function.</p><p><strong>Conclusions: </strong>Taken together, our results show that Abl1 plays an important role in AIS destabilization and that its activation compromises protein compartmentalization in a primary neuron culture model of AD.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative interpretable learning reveals shared patterns of epitranscriptomic regulation across multiple cancer types.","authors":"Xiangyu Yin, Gang Tu, Xuan Wang, Yuqi Liu, Yue Wang, Jiongming Ma, XiaoXuan Yu, Jia Meng, Bowen Song","doi":"10.1186/s12915-026-02628-1","DOIUrl":"10.1186/s12915-026-02628-1","url":null,"abstract":"<p><strong>Background: </strong>Cancer is a complex set of diseases caused by the dysregulation of cell proliferation, differentiation, and apoptosis, ultimately leading to malignant tumor development and metastasis. Recent studies have revealed that dysregulation of N4-acetylcytidine (ac⁴C) acetylation is associated with enhanced metastatic potential and tumor progression in various cancer types. However, it remains unclear whether diverse cancer types share common epitranscriptomic regulatory patterns or engage in interconnected networks.</p><p><strong>Results: </strong>In this study, leveraging an extensive collection of 88 ac⁴C epitranscriptome datasets profiled across multiple cancer types and normal conditions, we developed the first ac⁴C pan-cancer model by integrating a diverse set of sequence and curated genome-derived knowledge, based on a combined deep learning-powered transformer architecture. Our interpretable analysis uncovered, for the first time, the shared epitranscriptomic patterns and associations of dysregulated ac⁴C across different cancers, particularly associated with low GC-content regions of the 3'UTR and internal 3'UTR splicing. Furthermore, we discovered a set of candidate ac⁴C-mediated genes that may function in cancers through epitranscriptomic regulation, including three novel ac⁴C-mediated candidates (SMARCD1, SENP5, RNF207) that exhibit consistently dysregulated ac⁴C levels, expression patterns, and are associated with poor clinical prognosis across different cancer types.</p><p><strong>Conclusions: </strong>Taken together, our findings highlight the importance of a comprehensive characterization of ac⁴C epitranscriptome in pan-cancer landscape, with potential implications for developing RNA modification-based biomarkers and therapeutic strategies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated genomics and transcriptomics reveal key events in pancreatic neuroendocrine neoplasm.","authors":"Shiwei Guo, Xiaohan Shi, Xiaoyi Yin, Suizhi Gao, Bo Li, Huan Wang, Yikai Li, Beilei Wang, Xiongfei Xu, Kailian Zheng, Bin Song, Wei Jing, Chengli Song, Gang Jin","doi":"10.1186/s12915-026-02637-0","DOIUrl":"10.1186/s12915-026-02637-0","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuroendocrine neoplasm (PanNEN) represents the second most common epithelial neoplasm of the pancreas, characterized by remarkable heterogeneity among its subtypes. This study aimed to comprehensively characterize the molecular landscape of PanNENs and identify key features associated with tumor progression and therapeutic implications.</p><p><strong>Results: </strong>We performed an integrated molecular analysis of 106 PanNEN samples using whole-genome sequencing, whole-exome sequencing, and transcriptome sequencing. PanNEC demonstrated significantly higher mutation burden compared to PanNET, with recurrent mutations in KRAS and TP53. In metastatic PanNET, structural variation rearrangement signatures (RS) emerged as crucial molecular events affecting tumor-related gene expression. Copy number variation (CNV) analysis revealed four distinct PanNET subgroups: chromosomal-scale loss of heterozygosity (LOH), limited CNV events, whole-genome duplication (WGD), and WGD with chromosomal-scale LOH. We proposed a novel evolutionary model for PanNET based on CNV patterns, validated through transcriptomic analysis and clinical sampling. WGD was identified as a pivotal event in PanNET progression, significantly enhancing tumor aggressiveness. Transcriptomic profiling revealed distinct immune signatures associated with RS subtypes and WGD status, with the RS2 subtype showing a particularly favorable immune profile suggesting potential immunotherapy responsiveness.</p><p><strong>Conclusions: </strong>In summary, our systematic genomic and transcriptomic analyses revealed distinct biological features among PanNEN subtypes and identified a novel CNV-based evolutionary trajectory in PanNET. We demonstrated that structural variation and whole-genome duplication were critical events driving PanNET progression, providing new insights into PanNET biology with potential clinical implications.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITMol: a molecular image-text foundation model bridging the semantic gap for property prediction and retrieval.","authors":"Xuan Lin, Yang Sun, Luming Chen, Xiang Zhang, Lichang Dai, Haowen Chen, Hongxin Xiang, Zuguo Yu","doi":"10.1186/s12915-026-02627-2","DOIUrl":"10.1186/s12915-026-02627-2","url":null,"abstract":"<p><strong>Background: </strong>Multimodal foundation models demonstrate remarkable understanding ability to perform accurate molecular representation, including SMILES sequence-text and molecular graph-text representations. Molecular images represent another molecular modality that provides a more intuitive way to capture the spatial structural relationships of molecules. Existing models suffer from integrating image-text modalities for molecular property prediction, largely due to (1) the scarcity of high-quality image-text paired datasets, as existing molecular databases predominantly contain structural representations (SMILES, graphs) with limited descriptive text tailored for visual molecular understanding, and (2) the fundamental semantic gap between molecular images and textual descriptions, where complex visual features must be precisely aligned with domain chemical terminology and functional descriptions.</p><p><strong>Results: </strong>In this study, we present a molecular image-text foundation model, named ITMol, pretrained on 500k molecular image-text pairs. Specifically, ITMol addresses the scarcity of high-quality image-text paired datasets by constructing a comprehensive dataset through collection from chemical databases and automated generation using MolT5 to create high-quality image-text pairs, and tackles the fundamental semantic gap between molecular images and textual descriptions by implementing a sophisticated cross-attention mechanism designed specifically for molecular modalities, coupled with three complementary self-supervised learning strategies. We demonstrate the high performance of ITMol in molecular property prediction across 8 benchmark datasets, achieving an ROC-AUC score of 0.885 on the BBBP dataset. ITMol shows high R@5 scores on a dataset of 100k molecules in the cross-modal retrieval task. We further illustrate interpretability of ITMol using key chemical structures and functional groups.</p><p><strong>Conclusions: </strong>ITMol provides an effective framework for integrating 2D molecular images and molecular textual descriptions. The results show that image-text multimodal pretraining can improve molecular representation learning for property prediction and retrieval, offering a useful direction for multimodal molecular modeling.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sibling cooperation in boreal owls during the post-fledging dependence period.","authors":"Marek Kouba, Simona Stehlíková Sovadinová, Filip Tulis, Michal Ševčík, Jitka Bartošová, Erkki Korpimäki, Luděk Bartoš","doi":"10.1186/s12915-026-02626-3","DOIUrl":"10.1186/s12915-026-02626-3","url":null,"abstract":"<p><strong>Background: </strong>Many vertebrates develop in the company of their siblings, a social context that profoundly influences their life histories and phenotypes. While avian begging behaviour in parent-offspring conflict and sibling competition/cooperation have been largely studied in nestlings, the fledglings' begging remains under-researched, despite the continued dependency of young birds throughout the post-fledging dependence period (PFDP). Siblings typically maintain close proximity during the PFDP, a pattern that might be explained by the following four mutually non-exclusive hypotheses: competition over the prey delivered by parents (competition, H1), mutual affection established during the nestling period (cooperation-friendship, H2), various antipredation behaviours (cooperation-antipredation, H3) or begging negotiation about whose need is greater (cooperation-negotiation, H4).</p><p><strong>Results: </strong>We radio-tracked 123 boreal owl (Aegolius funereus) fledglings from 34 nests over 6 years in Czechia and Finland and recorded daily inter-sibling distances throughout the PFDP. Distances were longer in Czechia than in Finland during both night (82 ± 81 vs 56 ± 65 m; mean ± SD) and day (75 ± 109 vs 64 ± 86 m). In both areas, distances increased with an augmenting time gap in tracking, siblings' age and the number of present siblings at night but decreased during the day. These consistent patterns across different environments indicate that the life history of the target species prevails over the environmental effects. Consistent with the predictions of the cooperation-antipredation hypothesis (H3), the mean inter-sibling distances were shorter in Finland compared to Czechia during both day and night, and inter-sibling distances were shorter within larger sibling flocks during the day. The cooperation-negotiation hypothesis (H4) is supported by the finding that vocally begging siblings were closer to each other than their non-begging counterparts.</p><p><strong>Conclusions: </strong>Our results demonstrate, for the first time, that sibling cooperation can occur during the PFDP, when offspring are vulnerable to predators, both during diurnal roosting and at night while begging for food. We conclude that the inter-sibling distances in boreal owls during the PFDP are maintained because siblings cooperate through collective antipredation behaviour during diurnal roosting and through collective negotiation over access to the indivisible prey items delivered by their parent during nocturnal activity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phasic modulation of attentional rhythmic sampling according to task demands.","authors":"Qing Kong, Tong Wang, Jianrong Jia","doi":"10.1186/s12915-026-02630-7","DOIUrl":"10.1186/s12915-026-02630-7","url":null,"abstract":"<p><strong>Background: </strong>Attention is thought to periodically allocate cognitive resources to task-relevant stimuli, enabling the sequential sampling of multiple stimuli over time. However, whether the specific task influences the temporal dynamics of attentional sampling remains not fully understood.</p><p><strong>Results: </strong>This study investigates the dynamics of attentional sampling and how these dynamics are influenced by task demands, using high-frequency steady-state visual evoked potentials (SSVEPs). Participants were instructed to either select one of two visual stimuli or integrate both stimuli into a single target, with the stimuli tagged at 42 Hz and 44 Hz, respectively. Analysis of the SSVEP envelopes revealed that attention periodically samples stimuli within the theta band (4-6 Hz) in both tasks. Notably, the phase relationship between the SSVEP envelopes differed across tasks: distinct phases were observed in the selection task, whereas similar phases were found in the integration task. This task-dependent phase modulation was mediated by theta-band neural oscillations in the brain. Furthermore, the phase difference between SSVEP envelopes correlated with behavioral performance in the integration task but not in the selection task.</p><p><strong>Conclusions: </strong>These findings demonstrate a flexible, task-dependent mechanism for rhythmic attentional sampling, wherein neural oscillations align stimulus processing according to the specific demands of the task.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-driven adaptive radiation and host usage in sponge-associated barnacles.","authors":"Meng-Chen Yu, Hsiu-Chin Lin, Gregory A Kolbasov, Jens T Høeg, Benny K K Chan","doi":"10.1186/s12915-026-02618-3","DOIUrl":"10.1186/s12915-026-02618-3","url":null,"abstract":"<p><strong>Background: </strong>Adaptive radiation often involves ecological and morphological diversification, influenced by environmental opportunities, such as symbiotic interactions. Sponge-associated barnacles have evolved specialized traits, such as modified shells, to thrive within sponge hosts. However, the evolutionary mechanisms driving their diversification and host specificity remain unclear.</p><p><strong>Results: </strong>We integrate molecular phylogenetics (12S, 16S, 18S, COI, H3), detailed morphology, and ecological assessment to examine how host usage influences sponge-associated barnacle diversification. Our findings reveal two primary barnacle clades: Membranous-Base (M-Base) and Calcareous-Base (C-Base), each exhibiting distinct morphological adaptations. Most of the species exhibit strong host specificity being specialists within particular sponges. However, there is no significant correlation between morphology and host specificity, nor a clear co-evolutionary pattern with sponge hosts. These results challenge the assumption that host-driven specialization alone explains diversification.</p><p><strong>Conclusions: </strong>Our findings suggest that sponge-associated barnacles show a pattern of host-associated divergence, with generalist species occupying basal positions and specialization evolving from ancestrally broader host-use states. The last common ancestor of sponge barnacles appears to have been associated with Clionaida sponges, which may serve as permissive hosts due to their lower biochemical diversity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 rise in prepubertal DHEA in the spiny mouse reveals the effect of adrenarche on the reproductive axis.","authors":"Maya Sudman, Hadas Gruber, Ben Bar-Sadeh, Tal Refael, Gil Golan, Nicol Shvartsman, Lilach Pnueli, Noga Kronfeld-Schor, Philippa Melamed","doi":"10.1186/s12915-026-02619-2","DOIUrl":"10.1186/s12915-026-02619-2","url":null,"abstract":"<p><strong>Background: </strong>Adrenarche, characterized by rising adrenal dehydroepiandrosterone (DHEA) levels, precedes puberty and has been implicated in reproductive maturation, and disorders like polycystic ovary syndrome (PCOS). However, the mechanisms by which DHEA influences the hypothalamic-pituitary-gonadal (HPG) axis remain poorly understood, largely due to the absence of an appropriate animal model. The spiny mouse (genus Acomys), which has a prolonged juvenile phase and endogenous prepubertal DHEA production, provides a valuable system to investigate the effects of early-life exposure to DHEA.</p><p><strong>Results: </strong>We confirmed the spiny mouse prepubertal rise in circulating DHEA levels, which occurs independently of HPG axis activation, and concomitantly with increased expression of pituitary Prl and various ovarian steroidogenic and estrogen-responsive genes, including Prlr. In cultured cells, DHEA induced Prlr and Prl expression seemingly via the estrogen receptor. Adrenalectomy (Adx) revealed that DHEA is synthesized outside the adrenal glands, possibly the ovaries. Treatment of these mice with DHEA led to extensive changes in their ovarian transcriptomes, including upregulation of immune response-related genes, and downregulation of cholesterol metabolism and estrogen synthesis genes, most notably Cyp19a1. The reduced Cyp19a1 expression is likely due to the elevated Amhr2, and was accompanied by a high androgen-to-estrogen ratio, comprising DHEA-induced, PCOS-like characteristics.</p><p><strong>Conclusions: </strong>The rise in DHEA during an extended juvenile phase establishes the spiny mouse as a suitable model for studying the consequences of adrenarche. Our findings also reveal that increasing further these prepubertal DHEA levels alters ovarian gene expression and steroidogenesis, offering insights into how early androgen excess may predispose to reproductive dysfunction.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of vitellogenin receptor function results in yolk depletion, virome expansion, and reduced bacterial load within the oocytes of Rhodnius prolixus.","authors":"Juliana Amorim, Jéssica Pereira, Matheus das Neves, Thamara Rios, Cintia Lopes Nogueira, Valdir Braz, Leonan Reis, Allana Faria-Reis, Ana Beatriz Walter-Nuno, Lukas Selim, Daiene Nunes, Thalysson Vinícius de J C Baptista, Georgia C Atella, Marinella Silva Laport, Ana C Bahia, Carlos Logullo, Pedro L Oliveira, Gabriela O Paiva-Silva, Katia C Gondim, Isabela Ramos","doi":"10.1186/s12915-026-02622-7","DOIUrl":"10.1186/s12915-026-02622-7","url":null,"abstract":"<p><strong>Background: </strong>The vitellogenin receptor (VgR) mediates yolk protein uptake during follicle development and is essential for embryogenesis in oviparous species. Here, we characterize the single Rhodnius prolixus VgR isoform and uncover an unexpected role in microbial regulation within the reproductive system.</p><p><strong>Results: </strong>The receptor displays a conserved LDLR-like structure and is highly expressed in early oocytes. RNAi-mediated VgR silencing caused defective yolk granule biogenesis, leading to the accumulation of the main yolk protein precursors, Vg and RHBP, in the hemolymph, yet oviposition and fertilization proceeded normally. The resulting eggs were yolk-depleted and non-viable. Remarkably, VgR knockdown reduced bacterial 16S rRNA levels in oocytes while promoting the expansion of several members of the core virome, a phenotype not reproduced by Vg silencing. Neither purified Vg nor changes in immune (defensin) or RNA interference pathways explained the microbial shifts.</p><p><strong>Conclusions: </strong>These findings indicate that VgR influences not only yolk endocytosis but is also associated with changes in microbial composition within developing oocytes. We propose that VgR may contribute to a functional link between yolk endocytic dynamics and microbial homeostasis, thereby affecting the balance of microbial components in the oocyte. This connection broadens the functional context of VgR and provides new insight into how vertical transmission processes may be shaped in this major Chagas disease vector.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 ZEB1-Neon knock-in uncovers traceable dynamics of epithelial-mesenchymal transition in tumors in vivo.","authors":"Elisabetta D'Avanzo, Amelie Mahr, Nicolas Sauer, Simon Brandt, Ruthger van Roey, Harald Schuhwerk, Philipp Tripal, Benjamin Schmid, Stefanie Brey, Thomas H Winkler, Simone Brabletz, Thomas Brabletz, Marc P Stemmler","doi":"10.1186/s12915-026-02629-0","DOIUrl":"10.1186/s12915-026-02629-0","url":null,"abstract":"<p><strong>Background: </strong>Progression and metastasis of solid cancers are orchestrated by activation of epithelial-mesenchymal transition (EMT) in the primary tumor. This process is typically restricted to a limited number of cells that acquire partial or hybrid EMT states to unleash cellular plasticity. Capturing such dynamic and often reversible events in vivo on the single cell level is hampered by the lack of proper labeling tools that yet often induce permanent staining persisting beyond transient EMT activation.</p><p><strong>Methods: </strong>To enable live-tracking of EMT in vivo, we utilized CRISPaint and homologous recombination to endogenously tag ZEB1, one key transcription factor to activate EMT during tumorigenesis. Using the bright fluorescent protein mNeonGreen, we generated ZEB1-Neon fusion knock-in alleles in MDA-MB-231 and MCF10A cells, as well as in mice.</p><p><strong>Results: </strong>We demonstrate that mNeonGreen fluorescence is suitable to faithfully report on ZEB1 expression in vitro over time, becomes properly upregulated by TGFβ, and allows separation of ZEB1hi and ZEB1lo cells to capture different cellular properties, e.g., handling of DNA damage. The fusion does not affect ZEB1 function as evident by proper EMT induction, embryogenesis, and tissue homeostasis when present homozygously. Moreover, introducing Zeb1-Neon into the KPC mouse model of pancreatic cancer permits tracking of ZEB1+ cells in precision-cut slices and time-lapse imaging of isolated tumor cells.</p><p><strong>Conclusions: </strong>In summary, we provide a versatile tool that allows precise detection and live cell imaging of EMT, which will help to more accurately decipher the role of EMT in tumor progression and to identify therapeutic agents that can specifically manipulate EMT for novel combination therapies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"24 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13170155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}