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Retraction: Sheltering of deleterious mutations explains the stepwise extension of recombination suppression on sex chromosomes and other supergenes. 撤回:有害突变的庇护解释了性染色体和其他超基因上重组抑制的逐步扩展。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-27 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003106
{"title":"Retraction: Sheltering of deleterious mutations explains the stepwise extension of recombination suppression on sex chromosomes and other supergenes.","authors":"","doi":"10.1371/journal.pbio.3003106","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003106","url":null,"abstract":"","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003106"},"PeriodicalIF":9.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center in Drosophila. 背扇形体是果蝇的一个神经化学异质性睡眠调节中心。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-26 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003014
Joseph D Jones, Brandon L Holder, Andrew C Montgomery, Chloe V McAdams, Emily He, Anna E Burns, Kiran R Eiken, Alex Vogt, Adriana I Velarde, Alexandra J Elder, Jennifer A McEllin, Stephane Dissel
{"title":"The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center in Drosophila.","authors":"Joseph D Jones, Brandon L Holder, Andrew C Montgomery, Chloe V McAdams, Emily He, Anna E Burns, Kiran R Eiken, Alex Vogt, Adriana I Velarde, Alexandra J Elder, Jennifer A McEllin, Stephane Dissel","doi":"10.1371/journal.pbio.3003014","DOIUrl":"10.1371/journal.pbio.3003014","url":null,"abstract":"<p><p>Sleep is a behavior that is conserved throughout the animal kingdom. Yet, despite extensive studies in humans and animal models, the exact function or functions of sleep remain(s) unknown. A complicating factor in trying to elucidate the function of sleep is the complexity and multiplicity of neuronal circuits that are involved in sleep regulation. It is conceivable that distinct sleep-regulating circuits are only involved in specific aspects of sleep and may underlie different sleep functions. Thus, it would be beneficial to assess the contribution of individual circuits in sleep's putative functions. The intricacy of the mammalian brain makes this task extremely difficult. However, the fruit fly Drosophila melanogaster, with its simpler brain organization, available connectomics, and unparalleled genetics, offers the opportunity to interrogate individual sleep-regulating centers. In Drosophila, neurons projecting to the dorsal fan-shaped body (dFB) have been proposed to be key regulators of sleep, particularly sleep homeostasis. We recently demonstrated that the most widely used genetic tool to manipulate dFB neurons, the 23E10-GAL4 driver, expresses in 2 sleep-regulating neurons (VNC-SP neurons) located in the ventral nerve cord (VNC), the fly analog of the vertebrate spinal cord. Since most data supporting a role for the dFB in sleep regulation have been obtained using 23E10-GAL4, it is unclear whether the sleep phenotypes reported in these studies are caused by dFB neurons or VNC-SP cells. A recent publication replicated our finding that 23E10-GAL4 contains sleep-promoting neurons in the VNC. However, it also proposed that the dFB is not involved in sleep regulation at all, but this suggestion was made using genetic tools that are not dFB-specific and a very mild sleep deprivation protocol. In this study, using a newly created dFB-specific genetic driver line, we demonstrate that optogenetic activation of the majority of 23E10-GAL4 dFB neurons promotes sleep and that these neurons are involved in sleep homeostasis. We also show that dFB neurons require stronger stimulation than VNC-SP cells to promote sleep. In addition, we demonstrate that dFB-induced sleep can consolidate short-term memory (STM) into long-term memory (LTM), suggesting that the benefit of sleep on memory is not circuit-specific. Finally, we show that dFB neurons are neurochemically heterogeneous and can be divided in 3 populations. Most dFB neurons express both glutamate and acetylcholine, while a minority of cells expresses only one of these 2 neurotransmitters. Importantly, dFB neurons do not express GABA, as previously suggested. Using neurotransmitter-specific dFB tools, our data also points at cholinergic dFB neurons as particularly potent at regulating sleep and sleep homeostasis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003014"},"PeriodicalIF":9.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On improving the sustainability of peer review. 关于提高同行评议的可持续性。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-25 DOI: 10.1371/journal.pbio.3003127
Daniel Routledge, Nonia Pariente
{"title":"On improving the sustainability of peer review.","authors":"Daniel Routledge, Nonia Pariente","doi":"10.1371/journal.pbio.3003127","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003127","url":null,"abstract":"<p><p>The term \"reviewer fatigue\" has become only too familiar in scientific publishing. How can we ease the burden on reviewers to make the peer review system more sustainable, while streamlining the publication process for authors?</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003127"},"PeriodicalIF":9.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Navigation strategies in Caenorhabditis elegans are differentially altered by learning. 秀丽隐杆线虫的导航策略会因学习而发生不同的改变。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-21 DOI: 10.1371/journal.pbio.3003005
Kevin S Chen, Anuj K Sharma, Jonathan W Pillow, Andrew M Leifer
{"title":"Navigation strategies in Caenorhabditis elegans are differentially altered by learning.","authors":"Kevin S Chen, Anuj K Sharma, Jonathan W Pillow, Andrew M Leifer","doi":"10.1371/journal.pbio.3003005","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003005","url":null,"abstract":"<p><p>Learned olfactory-guided navigation is a powerful platform for studying how a brain generates goal-directed behaviors. However, the quantitative changes that occur in sensorimotor transformations and the underlying neural circuit substrates to generate such learning-dependent navigation is still unclear. Here we investigate learned sensorimotor processing for navigation in the nematode Caenorhabditis elegans by measuring and modeling experience-dependent odor and salt chemotaxis. We then explore the neural basis of learned odor navigation through perturbation experiments. We develop a novel statistical model to characterize how the worm employs two behavioral strategies: a biased random walk and weathervaning. We infer weights on these strategies and characterize sensorimotor kernels that govern them by fitting our model to the worm's time-varying navigation trajectories and precise sensory experiences. After olfactory learning, the fitted odor kernels reflect how appetitive and aversive trained worms up- and down-regulate both strategies, respectively. The model predicts an animal's past olfactory learning experience with  > 90% accuracy given finite observations, outperforming a classical chemotaxis metric. The model trained on natural odors further predicts the animals' learning-dependent response to optogenetically induced odor perception. Our measurements and model show that behavioral variability is altered by learning-trained worms exhibit less variable navigation than naive ones. Genetically disrupting individual interneuron classes downstream of an odor-sensing neuron reveals that learned navigation strategies are distributed in the network. Together, we present a flexible navigation algorithm that is supported by distributed neural computation in a compact brain.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003005"},"PeriodicalIF":9.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken. 在体内,sonic hedgehog通路的拮抗作用暂时导致鸡祖先的原始羽毛样结构。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-20 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003061
Rory L Cooper, Michel C Milinkovitch
{"title":"In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken.","authors":"Rory L Cooper, Michel C Milinkovitch","doi":"10.1371/journal.pbio.3003061","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003061","url":null,"abstract":"<p><p>The morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning and morphogenesis. In particular, the sonic hedgehog (Shh) pathway is an important mediator of feather outgrowth and branching. However, functional in vivo evidence regarding its role during feather development remains limited. Here, we demonstrate that an intravenous injection of sonidegib, a potent Shh pathway inhibitor, at embryonic day 9 (E9) temporarily produces striped domains (instead of spots) of Shh expression in the skin, arrests morphogenesis, and results in unbranched and non-invaginated feather buds-akin to proto-feathers-in embryos until E14. Although feather morphogenesis partially recovers, hatched treated chickens exhibit naked skin regions with perturbed follicles. Remarkably, these follicles are subsequently reactivated by seven weeks post-hatching. Our RNA-sequencing data and rescue experiment using Shh-agonism confirm that sonidegib specifically down-regulates Shh pathway activity. Overall, we provide functional evidence for the role of the Shh pathway in mediating feather morphogenesis and confirm its role in the evolutionary emergence and diversification of feathers.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003061"},"PeriodicalIF":9.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced memory despite severe sleep loss in Drosophila insomniac mutants. 失眠症突变果蝇在严重睡眠不足的情况下记忆力增强。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-20 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003076
Sheng Huang, Chengji Piao, Zhiying Zhao, Christine B Beuschel, Oriane Turrel, David Toppe, Stephan J Sigrist
{"title":"Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.","authors":"Sheng Huang, Chengji Piao, Zhiying Zhao, Christine B Beuschel, Oriane Turrel, David Toppe, Stephan J Sigrist","doi":"10.1371/journal.pbio.3003076","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003076","url":null,"abstract":"<p><p>Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced memory. Through a genetic modifier screen, we found that a mild reduction of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes of inc mutants. However, this reduction further increased their excessive memory and mushroom body overgrowth. Since inc mutants displayed higher PKA signaling, we propose that inc loss-of-function suppresses sleep via increased PKA activity, which also constrains the excessive memory of inc mutants. Our data identify a signaling cascade for balancing sleep and memory functions, and provide a plausible explanation for the sleep phenotypes of inc mutants, suggesting that memory hyperfunction can provoke sleep deficits.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003076"},"PeriodicalIF":9.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The IBEX Knowledge-Base: A central resource for multiplexed imaging techniques. IBEX知识库:多路成像技术的中心资源。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-19 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003070
Andrea J Radtke, Ifeanyichukwu U Anidi, Leanne Arakkal, Armando J Arroyo-Mejias, Rebecca T Beuschel, Katy Börner, Colin J Chu, Beatrice Clark, Menna R Clatworthy, Jake Colautti, Fabian Coscia, Joshua Croteau, Saven Denha, Rose Dever, Walderez O Dutra, Sonja Fritzsche, Spencer Fullam, Michael Y Gerner, Anita Gola, Kenneth J Gollob, Jonathan M Hernandez, Jyh Liang Hor, Hiroshi Ichise, Zhixin Jing, Danny Jonigk, Evelyn Kandov, Wolfgang Kastenmüller, Joshua F E Koenig, Rosa K Kortekaas, Aanandita Kothurkar, Alexandra Y Kreins, Ian T Lamborn, Yuri Lin, Katia Luciano Pereira Morais, Aleksandra Lunich, Jean C S Luz, Ryan B MacDonald, Chen Makranz, Vivien I Maltez, John E McDonough, Ryan V Moriarty, Juan M Ocampo-Godinez, Vitoria M Olyntho, Annette Oxenius, Kartika Padhan, Kirsten Remmert, Nathan Richoz, Edward C Schrom, Wanjing Shang, Lihong Shi, Rochelle M Shih, Emily Speranza, Salome Stierli, Sarah A Teichmann, Tibor Z Veres, Megan Vierhout, Brianna T Wachter, Adam K Wade-Vallance, Margaret Williams, Nathan Zangger, Ronald N Germain, Ziv Yaniv
{"title":"The IBEX Knowledge-Base: A central resource for multiplexed imaging techniques.","authors":"Andrea J Radtke, Ifeanyichukwu U Anidi, Leanne Arakkal, Armando J Arroyo-Mejias, Rebecca T Beuschel, Katy Börner, Colin J Chu, Beatrice Clark, Menna R Clatworthy, Jake Colautti, Fabian Coscia, Joshua Croteau, Saven Denha, Rose Dever, Walderez O Dutra, Sonja Fritzsche, Spencer Fullam, Michael Y Gerner, Anita Gola, Kenneth J Gollob, Jonathan M Hernandez, Jyh Liang Hor, Hiroshi Ichise, Zhixin Jing, Danny Jonigk, Evelyn Kandov, Wolfgang Kastenmüller, Joshua F E Koenig, Rosa K Kortekaas, Aanandita Kothurkar, Alexandra Y Kreins, Ian T Lamborn, Yuri Lin, Katia Luciano Pereira Morais, Aleksandra Lunich, Jean C S Luz, Ryan B MacDonald, Chen Makranz, Vivien I Maltez, John E McDonough, Ryan V Moriarty, Juan M Ocampo-Godinez, Vitoria M Olyntho, Annette Oxenius, Kartika Padhan, Kirsten Remmert, Nathan Richoz, Edward C Schrom, Wanjing Shang, Lihong Shi, Rochelle M Shih, Emily Speranza, Salome Stierli, Sarah A Teichmann, Tibor Z Veres, Megan Vierhout, Brianna T Wachter, Adam K Wade-Vallance, Margaret Williams, Nathan Zangger, Ronald N Germain, Ziv Yaniv","doi":"10.1371/journal.pbio.3003070","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003070","url":null,"abstract":"<p><p>Multiplexed imaging is a powerful approach in spatial biology, although it is complex, expensive and labor-intensive. Here, we present the IBEX Knowledge-Base, a central resource for reagents, protocols and more, to enhance knowledge sharing, optimization and innovation of spatial proteomics techniques.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003070"},"PeriodicalIF":9.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Past conservation efforts reveal which actions lead to positive outcomes for species. 过去的保护工作揭示了哪些行动会给物种带来积极的结果。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-18 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003051
Ashley T Simkins, William J Sutherland, Lynn V Dicks, Craig Hilton-Taylor, Molly K Grace, Stuart H M Butchart, Rebecca A Senior, Silviu O Petrovan
{"title":"Past conservation efforts reveal which actions lead to positive outcomes for species.","authors":"Ashley T Simkins, William J Sutherland, Lynn V Dicks, Craig Hilton-Taylor, Molly K Grace, Stuart H M Butchart, Rebecca A Senior, Silviu O Petrovan","doi":"10.1371/journal.pbio.3003051","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003051","url":null,"abstract":"<p><p>Understanding the consequences of past conservation efforts is essential to inform the means of maintaining and restoring species. Data from the IUCN Red List for 67,217 animal species were reviewed and analyzed to determine (i) which conservation actions have been implemented for different species, (ii) which types of species have improved in status and (iii) which actions are likely to have driven the improvements. At least 51.8% (34,847) of assessed species have actions reported, mostly comprising protected areas (82.7%). Proportionately more actions were reported for tetrapods and warm-water reef-building corals, and fewer for fish, dragonflies and damselflies and crustaceans. Species at greater risk of extinction have a wider range of species-targeted actions reported compared with less threatened species, reflecting differences in documentation and conservation efforts. Six times more species have deteriorated than improved in status, as reflected in their IUCN Red List category. Almost all species that improved have conservation actions in place, and typically were previously at high risk of extinction, have smaller ranges and were less likely to be documented as threatened by hunting and habitat loss or degradation. Improvements in status were driven by a wide range of actions, especially reintroductions; for amphibians and birds, area management was also important. While conservation interventions have reduced the extinction risk of some of the most threatened species, in very few cases has full recovery been achieved. Scaling up the extent and intensity of conservation interventions, particularly landscape-scale actions that benefit broadly distributed species, is urgently needed to assist the recovery of biodiversity.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003051"},"PeriodicalIF":9.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbiota isolate collections: A key to global vector-borne disease control. 分离微生物群收集:全球媒介传播疾病控制的关键。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-18 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003078
Miguel Medina Muñoz, Holly L Nichols, Kerri L Coon
{"title":"Microbiota isolate collections: A key to global vector-borne disease control.","authors":"Miguel Medina Muñoz, Holly L Nichols, Kerri L Coon","doi":"10.1371/journal.pbio.3003078","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003078","url":null,"abstract":"<p><p>Insect vector microbiomes are essential for insect function, making them promising targets for controlling vector-borne diseases. Microbial isolate collections aid in identifying microbial targets, but expanding these collections must rely on coordinated efforts that are ethical and ensure equitable benefit sharing.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003078"},"PeriodicalIF":9.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The end of the genetic paradigm of cancer. 癌症基因模式的终结。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-03-18 eCollection Date: 2025-03-01 DOI: 10.1371/journal.pbio.3003052
Sui Huang, Ana M Soto, Carlos Sonnenschein
{"title":"The end of the genetic paradigm of cancer.","authors":"Sui Huang, Ana M Soto, Carlos Sonnenschein","doi":"10.1371/journal.pbio.3003052","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003052","url":null,"abstract":"<p><p>Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea that cancer is a 'genetic disease', as posited by the somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis is caused by cancer-driving somatic mutations and clonal expansion. However, results from tumor sequencing, motivated by the genetic paradigm itself, create apparent 'paradoxes' that are not conducive to a pure SMT. But beyond genetic causation, the new results lend credence to old ideas from organismal biology. To resolve inconsistencies between the genetic paradigm of cancer and biological reality, we must complement deep sequencing with deep thinking: embrace formal theory and historicity of biological entities, and (re)consider non-genetic plasticity of cells and tissues. In this Essay, we discuss the concepts of cell state dynamics and tissue fields that emerge from the collective action of genes and of cells in their morphogenetic context, respectively, and how they help explain inconsistencies in the data in the context of SMT.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003052"},"PeriodicalIF":9.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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