PLoS Biology最新文献

{"title":"Regeneration programs buffer genetic defects in animal development.","authors":"Kazunori Ando, Sushant Bangru, John Welsby, John D Thompson, Kenneth D Poss","doi":"10.1371/journal.pbio.3004011","DOIUrl":"10.1371/journal.pbio.3004011","url":null,"abstract":"<p><p>Regeneration programs enable animals to restore damaged or lost tissues, and the range of stimuli for these programs is incompletely understood. Here, we used zebrafish, a vertebrate species with exceptional regenerative capacity, to identify chemically induced mutations that alter regeneration-associated gene activation. Transgenic zebrafish with a permissive promoter and EGFP cassette inserted in the vicinity of the pro-regenerative factor gene fgf20a were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in fgf20a-directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated fgf20a:EGFP presence in the absence of experimental injury, localized to regions of fin fold tissue undergoing degeneration. Whole-genome sequencing identified a mutation within exon 72 of the fraser syndrome 1 (fras1) gene, mutated in patients with inherited skin disease. fras1 mutant larvae spontaneously displayed broader signatures of regeneration, and zebrafish crispants for homologs of other genes mutated in human developmental diseases also displayed regeneration-associated gene expression in regions of dysmorphology. Tempering Fgf signaling by transgenic expression of a dominant-negative Fgf receptor in fras1 mutants exacerbated the disease phenotype. Our findings provide evidence that regeneration programs are harnessed in response to developmental defects caused by genetic mutations, potentially buffering deleterious phenotypes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004011"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018457","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":"The kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei.","authors":"Bianca Manuela Berger, Enrico Santini, Himaja Manjunatha, Lea Trost, Markus Gerber, Hauke S Hillen, Torsten Ochsenreiter","doi":"10.1371/journal.pbio.3003945","DOIUrl":"10.1371/journal.pbio.3003945","url":null,"abstract":"<p><p>Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP, Tb927.11.5780) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1, Tb927.6.4510) in the Kinetoplastea. The mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein results in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. mTF1 specifically binds to kDNA and since it is unique to the Kinetoplastea, it might prove to be a promising drug target.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003945"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018432","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":"Gene flow drives periods of both evolutionary stasis and change in a wild bird population.","authors":"Simon R Evans, Henri Bouwmeester, Arie J van Noordwijk, Marcel E Visser, Erik Postma","doi":"10.1371/journal.pbio.3004004","DOIUrl":"10.1371/journal.pbio.3004004","url":null,"abstract":"<p><p>The struggle to explain the absence of evolutionary change in heritable, fitness-related traits of free-living populations has become emblematic of our ignorance of the evolutionary process in the wild. Yet while this 'paradox of stasis' has been the subject of much discussion, it is primarily identified a posteriori and rarely subject to direct quantification. We examined the evolution of clutch size in neighbouring populations of great tits (Parus major) before, during and after an experimental evolutionary perturbation. Interannual genetic changes in clutch size were directionally consistent with selection (refuting absolute stasis) but were smaller than predicted by adaptive evolutionary models (supporting relative stasis). Yet accounting for the contribution of post-selective immigration (i.e., explicitly recognising the distinction between adaptation and evolution) greatly improved our forecast accuracy and this tendency toward overprediction. Indeed, attributing interannual genetic change to its contributing demographic processes revealed immigration to be key to explaining periods of both evolutionary stasis and change, with its evolutionary impact varying across time and space in a manner analogous to the dynamism of natural selection. Our multi-decadal study of clutch size evolution thus shows that recognising the impact of gene flow is crucial to explaining contemporary evolutionary change and stasis of a key determinant of life history.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004004"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018489","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":"Regional signaling controls stem cell-mediated regeneration in an invertebrate chordate.","authors":"Tal Gordon, Tom Levy, Chester Jiamu Yu, Benyamin Rosental, Lauren Lubeck, Lucia Manni, Irving L Weissman, Ayelet Voskoboynik","doi":"10.1371/journal.pbio.3004000","DOIUrl":"10.1371/journal.pbio.3004000","url":null,"abstract":"<p><p>Many tissues harbor quiescent stem cells that activate after injury, yet how local signals regulate this transition is not well understood. The solitary ascidian Ciona robusta provides a unique model, as bottom body fragments regenerate while upper fragments fail to do so. By comparing these regenerative and non-regenerative contexts, we reveal striking differences in transcriptional dynamics and signaling environments. Combining flow cytometry, scRNA-seq, transplantation, and fate mapping, we identified a candidate stem cell population with robust proliferative and differentiation potential following transplantation. However, regenerative capacity does not simply reflect stem cell abundance, but instead depends on region-specific signaling cues. Local expression of metabolic, immune and differentiation-related factors further underscores the importance of spatially distinct environments in shaping outcomes. Our findings show how a shared injury response is associated with divergent regenerative outcomes, highlighting principles that may inform strategies to enhance tissue repair in other systems.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004000"},"PeriodicalIF":7.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002716","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":"Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation.","authors":"Mona Nazemi, Bian Yanes, Eric Vancauwenberghe, Ifeoluwa Oyelade, Heather Walker, Elena Rainero","doi":"10.1371/journal.pbio.3003555","DOIUrl":"10.1371/journal.pbio.3003555","url":null,"abstract":"<p><p>Invasive breast and pancreatic cancer cells thrive within a collagen I-rich, poorly perfused extracellular matrix (ECM) network, necessitating robust metabolic adaptation to endure nutrient deficiency, such as glucose starvation. Here we demonstrate that collagen I is critical for the survival and growth of breast and pancreatic cancer cells. Mechanistically, collagen I promotes α2 β1 integrin-dependent S6 phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) and drives the membrane localisation of the LAT1-4F2hc amino acid transporter. This process ensures a sustained intracellular essential amino acid supply, further fuelling mTORC1 signalling and limiting autophagy. This collagen I-driven pathway is essential for cancer cell survival, as inhibiting the activity of α2 β1 integrin or the LAT1-4F2hc transporter significantly reduces cell growth and invasion in both 2D and 3D models. Finally, the clinical relevance of these transporters is underscored by the significant upregulation of LAT1-4F2hc expression in basal-like breast and pancreatic cancer patients, correlating with poor prognosis and drug resistance. Collectively, our findings highlight that targeting the LAT1-4F2hc transporter might represent a highly promising therapeutic strategy to limit cancer cell growth and invasion in highly fibrotic and nutrient-deprived tumours.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003555"},"PeriodicalIF":7.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002632","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":"SpaMOAL is a deep learning method that enables accurate spatial domain identification from multi-omics data.","authors":"Jinxia Wang, Yuying Huo, Rui Zhao, Yan Pan, Jianqiang Wu, Han Wang, Xiangyu Li","doi":"10.1371/journal.pbio.3003690","DOIUrl":"10.1371/journal.pbio.3003690","url":null,"abstract":"<p><p>Recent advances in spatial multi-omics technologies have opened new avenues for characterizing tissue architecture and function in situ, by simultaneously providing multimodal and complementary information-such as spatially resolved transcriptomic, epigenomic, and proteomic features. Current computational approaches face substantial challenges, such as effective integration of multi-omics molecular information with spatial information and corresponding high-resolution histology images. To address this challenge, we proposed SpaMOAL (Spatially Multi-Omics graph contrAstive Learning), a graph-based contrastive learning approach for spatial domain identification. SpaMOAL learns clustering-friendly representations from spatial multi-omics data by integrating spatial coordinates, histological image features, and molecular profiles, enabling accurate delineation of spatial tissue domains. Benchmarking across multiple recent paired spatial multi-omics datasets from mouse and human demonstrated that SpaMOAL consistently outperforms existing methods. By enabling accurate spatial domain delineation, SpaMOAL provides a powerful framework for interpreting tissue organization and cellular microenvironments.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003690"},"PeriodicalIF":7.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983932","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":"Turning a phage anti-defense weapon into an immunity trigger.","authors":"Anna B Adelstein, Naama Aviram","doi":"10.1371/journal.pbio.3003978","DOIUrl":"10.1371/journal.pbio.3003978","url":null,"abstract":"<p><p>Most bacterial immune systems raise an alarm when they sense a phage. A new study in PLOS Biology shows how type II Panoptes reverses this logic by maintaining a quiet signal and sensing infection through its sudden disappearance.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003978"},"PeriodicalIF":7.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983906","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":"An engineered bacterial symbiont maps micron-scale sugar gradients in the honeybee gut.","authors":"Audam Chhun, Andrew Quinn, Alicia I Pérez-Lorente, Théodora Steiner, Florian Zoppi, Thi Huong Giang Nguyen, Philipp Engel, Yolanda Schaerli","doi":"10.1371/journal.pbio.3003997","DOIUrl":"10.1371/journal.pbio.3003997","url":null,"abstract":"<p><p>The honeybee gut microbiota plays a key role in shaping host health and susceptibility to disease. Yet, the nutrient environment it experiences within the gut remains poorly characterized. In particular, little is known about the spatial distribution of nutrients across the microbial community, as resolving such fine gradients in vivo has been technically challenging. Here, we engineer the native honeybee symbiont Snodgrassella alvi as a living biosensor to quantify the bioavailability of the dietary sugar arabinose within the gut. By expanding the genetic toolkit for S. alvi through chromosomal integration of high-burden genes and a suite of low-strength promoters, we achieve stable multi-gene expression without compromising host colonization. The resulting biosensor generates a specific, dose-dependent fluorescent response to arabinose in the living host, enabling visualization of sugar gradients across gut-associated bacterial biofilms at micron-scale resolution. Upon co-colonization with distinct Gilliamella species that differ in arabinose metabolism, the biosensor reported differential in vivo arabinose consumption, directly validating species-specific metabolic specialization within the host. Feeding bees with pollen further uncovered pronounced radial heterogeneity in the distribution of pollen-derived arabinose. These findings demonstrate how diet composition and microbial specialization generate fine-scale microenvironments within the gut. More broadly, this work establishes S. alvi as a genetically tractable platform for in situ biosensing, opening new avenues for dissecting metabolic interactions and nutrient distribution within living hosts.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003997"},"PeriodicalIF":7.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983930","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":"Atlastin-2-mediated endoplasmic reticulum membrane tethering is critical for flavivirus replication.","authors":"Jonathan Einterz Owen, Cheyanne Lynn Bemis, Qingyi Wang, Ambarish C Varadan, Jacob W Vander Velden, Laura Andačić, Olus Uyar, Mansi Gupta, Christopher D Scharer, Laurent Chatel-Chaix, Pietro Scaturro, Mehul S Suthar, Christopher J Neufeldt","doi":"10.1371/journal.pbio.3003556","DOIUrl":"10.1371/journal.pbio.3003556","url":null,"abstract":"<p><p>Flaviviruses (genus Orthoflavivirus) are arthropod-borne viruses which cause approximately 400 million annual global infections in humans. Flavivirus infection requires cellular machinery to facilitate replication and spread. All known flaviviruses replicate in association with the host endoplasmic reticulum (ER), where genome replication is confined within virus-induced ER invaginations called viral replication organelles (vROs). Despite the central role of these structures during flavivirus infection, the mechanisms underlying vRO biogenesis remain undefined-particularly the membrane rearrangements required for their formation. In this work, we report a conserved role for a cellular ER remodeling protein, atlastin-2 (ATL2), in the organization of vROs within infected cells. Using confocal and electron microscopy, we show that ATL2 depletion leads to a reduction in vRO spatial distribution in flavivirus-infected cells. Changes in vRO distribution corresponded with a decrease in virus production and robust induction of innate immune responses. We also demonstrate that ATL2 accumulates in areas of vRO formation during flavivirus infection. Critically, mutational analysis showed that a tethering-competent but fusion-defective ATL2 mutant was sufficient to rescue DENV and ZIKV replication in ATL2-knockout cells. Finally, targeting of ATL2 activity using synthetic peptides significantly reduced DENV replication in both immortalized and human primary cells, suggesting a possible avenue for targeting host ER functions to limit flavivirus replication. Taken together, these results show that membrane tethering plays a critical and conserved role in flavivirus infection, functioning to organize membranes for vRO biogenesis and limit cellular immune activation. Importantly, we provide evidence that ATL2-mediated membrane organization can be targeted to inhibit viral replication.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003556"},"PeriodicalIF":7.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978501","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":"Does acute inflammation triggered by infection promote cancer progression?","authors":"Felipe Valença-Pereira, Bryan Johnson, James DeGregori, Mercedes Rincon","doi":"10.1371/journal.pbio.3003962","DOIUrl":"10.1371/journal.pbio.3003962","url":null,"abstract":"<p><p>Chronic infections are associated with cancer incidence and progression in human epidemiological data, but less is known about how such infections might promote cancer progression. Recent data implicate acute infection with common respiratory viruses, such as influenza and SARS-CoV-2, in cancer progression, providing evidence that infection-driven inflammation can promote tumor expansion and dissemination in experimental systems. The resulting acute inflammatory cascade and dynamic immune cell reprogramming can rapidly remodel the tissue microenvironment to favor cancer cell survival, growth, and evasion of immune elimination. However, acute infections can also elicit anti-tumor immune responses. Defining how infections differentially skew immune programs to promote or restrain cancer progression will therefore be essential for developing future strategies to target this disease.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003962"},"PeriodicalIF":7.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978504","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}