PLoS Biology最新文献

{"title":"Two distinct subpopulations of human stem-like memory T cells exhibit complementary roles in self-renewal and clonal longevity.","authors":"Danai Koftori, Charandeep Kaur, Laura Mora Bitria, Yan Zhang, Linda Hadcocks, Ada W C Yan, Piotr F Burzyński, Kristin Ladell, Daniel E Speiser, Katrina M Pollock, Derek Macallan, Becca Asquith","doi":"10.1371/journal.pbio.3003179","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003179","url":null,"abstract":"<p><p>T stem cell-like memory cells (TSCM cells) are considered to be essential for the maintenance of immune memory. The TSCM population has been shown to have the key properties of a stem cell population: multipotency, self-renewal and clonal longevity. Here we show that no single population has all these stem cell properties, instead the properties are distributed. We show that the human TSCM population consists of two distinct cell subpopulations which can be distinguished by the level of their CD95 expression (CD95int and CD95hi). Crucially, using long-term in vivo labelling of human volunteers, we establish that these are distinct populations rather than transient states of the same population. These two subpopulations have different functional profiles ex vivo, different transcriptional patterns, and different tissue distributions. They also have significantly different TREC content indicating different division histories and we find that the frequency of CD95hi TSCM increases with age. Most importantly, CD95hi and CD95int TSCM cells also have very different dynamics in vivo with CD95hi cells showing considerably higher proliferation but significantly reduced clonal longevity compared with CD95int TSCM. While both TSCM subpopulations exhibit considerable multipotency, no single population of TSCM cells has both the properties of self-renewal and clonal longevity. Instead, the \"stemness\" of the TSCM population is generated by the complementary dynamic properties of the two subpopulations: CD95int TSCM which have the property of clonal longevity and CD95hi TSCM which have the properties of expansion and self-renewal. We suggest that together, these two populations function as a stem cell population.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003179"},"PeriodicalIF":9.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337172","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}

{"title":"Using anti-DEI policies to dismantle education: A new front in a really old battle.","authors":"Cissy J Ballen, Terry McGlynn, Kelly R Zamudio","doi":"10.1371/journal.pbio.3003256","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003256","url":null,"abstract":"<p><p>Educational equity faces renewed threats across higher education in the United States, undermining learning for all. What can the community of life science instructors and researchers do to prioritize equitable, evidence-based teaching?</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003256"},"PeriodicalIF":9.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337173","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}

{"title":"Single-nucleus transcriptomics of wing sexual dimorphism and scale cell specialization in sulphur butterflies.","authors":"Ling S Loh, Joseph J Hanly, Alexander Carter, Martik Chatterjee, Martina Tsimba, Donya N Shodja, Luca Livraghi, Christopher R Day, Robert D Reed, W Owen McMillan, Gregory A Wray, Arnaud Martin","doi":"10.1371/journal.pbio.3003233","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003233","url":null,"abstract":"<p><p>The evolution of sexual secondary characteristics necessitates regulatory factors that confer sexual identity to differentiating tissues and cells. In Colias eurytheme butterflies, males exhibit two specialized wing scale types-ultraviolet-iridescent (UVI) and spatulate scales-which are absent in females and likely integral to male courtship behavior. This study investigates the regulatory mechanisms and single-nucleus transcriptomics underlying these two sexually dimorphic cell types during wing development. We show that Doublesex (Dsx) expression is itself dimorphic and required to repress the UVI cell state in females, while unexpectedly, UVI activation in males is independent from Dsx. In the melanic marginal band, Dsx is required in each sex to enforce the presence of spatulate scales in males, and their absence in females. Single-nucleus RNAseq reveals that UVI and spatulate scale cell precursors each show distinctive gene expression profiles at 40% of pupal development, with marker genes that include regulators of transcription, cell signaling, cytoskeletal patterning, and chitin secretion. Both male-specific cell types share a low expression of the Bric-a-brac (Bab) transcription factor, a key repressor of the UVI fate. Bab ChIP-seq profiling suggests that Bab binds the cis-regulatory regions of gene markers associated to UVI fate, including potential effector genes involved in the regulation of cytoskeletal processes and chitin secretion, and loci showing signatures of recent selective sweeps in a UVI-polymorphic population. These findings open new avenues for exploring wing patterning and scale development, shedding light on the mechanisms driving the specification of sex-specific cell states and the differentiation of specialized cell ultrastructures.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003233"},"PeriodicalIF":9.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327487","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}

{"title":"Zebrafish sperm outsource activation to eggs' protease-activated receptors.","authors":"Rafael A Fissore, Emily M Lopes, Francesca Carpentiero","doi":"10.1371/journal.pbio.3003214","DOIUrl":"10.1371/journal.pbio.3003214","url":null,"abstract":"<p><p>The calcium surge that starts embryogenesis varies across species and is elusive in many. A new study in PLOS Biology shows that zebrafish eggs self-activate, initiating a protease-activated receptor calcium wave and uncovering a novel pathway in egg activation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003214"},"PeriodicalIF":9.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327488","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":"Auditory cortex neurons that encode negative prediction errors respond to omissions of sounds in a predictable sequence.","authors":"Amit Yaron, Tomoyo Shiramatsu-Isoguchi, Felix B Kern, Kenichi Ohki, Hirokazu Takahashi, Zenas C Chao","doi":"10.1371/journal.pbio.3003242","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003242","url":null,"abstract":"<p><p>Predictive coding posits the brain predicts incoming sensory information and signals a positive prediction error when the actual input exceeds what was predicted, and a negative prediction error when it falls short of the prediction. It is theorized that specific neurons encode the negative prediction error, distinct from those for the positive prediction error, and are linked to responses to omitted expected inputs. However, what information is actually encoded by omission responses remains unclear. This information is essential to confirm their role as negative prediction errors. Here, we record single-unit activity in the rat auditory cortex during an omission paradigm where tone probabilities are manipulated to vary the prediction content. We identify neurons that robustly respond to omissions, with responses that increase with evidence accumulation and directly correlate with tone predictability-key characteristics suggesting their role as negative prediction-error neurons. Interestingly, these neurons showed selective omission responses but broad tone responses, revealing an asymmetry in error signaling. To capture this asymmetry, we propose a circuit model composed of laterally interconnected prediction-error neurons that qualitatively reproduce the observed asymmetry. Furthermore, we demonstrate that these lateral connections enhance the precision and efficiency of prediction encoding across receptive fields, and that their validity is supported by the free energy principle.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003242"},"PeriodicalIF":9.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327486","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}

{"title":"Protease-mediated activation of Par2 elicits calcium waves during zebrafish egg activation and blastomere cleavage.","authors":"Jiajia Ma, Tom J Carney","doi":"10.1371/journal.pbio.3003181","DOIUrl":"10.1371/journal.pbio.3003181","url":null,"abstract":"<p><p>Successful initiation of animal development requires activation of the egg immediately prior to fusion of gamete pronuclei. In all taxa, this is initiated by waves of calcium transients which transverse across the egg. Calcium waves also occur at cleavage furrows during later blastula cytokinesis. Calcium is released from the endoplasmic reticulum through activation of inositol-1,4,5-trisphosphate (IP3) receptors. Only a subset of the mechanisms employed to generate IP3 during vertebrate egg activation are defined, with strong evidence that other critical mechanisms exist. Serine proteases have been long implicated in egg activation and fertilization. Here, we report that treatment of zebrafish eggs with serine protease inhibitors leads to defective calcium wave propagation and failed egg activation. We further show that mutation of zebrafish Protease-activated receptor 2a (Par2a) also results in severe disruption of egg activation, leading to failed chorion elevation and ooplasmic segregation. Milder par2a mutants progress further, but then show abnormal blastomere cleavage. We observed that par2a mutants show decreased amplitude and duration of calcium transients. Restoring Ca++ or direct injection of IP3 ligand rescues egg activation aborted by either serine protease inhibitor treatment or by mutation of Par2a. We thus show that serine protease activity is a critical regulator of IP3 and subsequent calcium wave amplification during zebrafish egg activation, and link this to intracellular calcium release via the protease receptor, Par2a. This constitutes a novel signaling pathway critical for successful fertilization.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003181"},"PeriodicalIF":9.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318463","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":"Precise spike-timing information in the brainstem is well aligned with the needs of communication and the perception of environmental sounds.","authors":"Chris Scholes, Stephen Coombes, Alan R Palmer, William S Rhode, Rob Mill, Christian J Sumner","doi":"10.1371/journal.pbio.3003213","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003213","url":null,"abstract":"<p><p>The dynamic fluctuations in the amplitude of sound, known as sound envelopes, are ubiquitous in natural sounds and convey information critical for the recognition of speech, and of sounds generally. We are perceptually most sensitive to slow modulations which are most common. However, previous studies of envelope coding in the brainstem found an under-representation of these slow, low-frequency, modulations. Specifically, the synchronization of spike times to the envelope was enhanced in some neuron types, forming channels specialized for envelope processing but tuned to a restricted range of fast, high-frequency, envelopes (200-500 Hz). Here, we show using a historical dataset from cats that previous analyses, which made strong assumptions about the neural code, underestimated the encoding of low-frequency envelopes. While some neurons encode envelope better than others, most encode a wide range of envelope frequencies, and represent slower envelope fluctuations most accurately in their precise patterns of spike times. Identification of envelope frequency from spike-timing was linked to reliability, and to the way that dynamics of spiking interacted with the time-varying envelope. In some of the best-performing neurons, temporally complex \"mode-locked\" spike patterns served to enhance envelope coding. A second long-standing contradiction was that neural envelope coding is degraded at high sound levels, whilst the perception of envelope is robust at a wide range of sound levels. We find that spike-time encoding of envelope shape becomes level-robust for small populations of neurons. These findings argue against feature-specific coding of envelopes in the brainstem, and for a distributed population spike-time code for which synchrony to the envelope is an incomplete description. This code is accurate for slow fluctuations and robust across sound level. Thus, precise spike-timing information in the brainstem is after-all aligned with the needs of communication and the perception of environmental sounds.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003213"},"PeriodicalIF":9.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310689","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}

{"title":"Nuances in the control of separase activity between mitosis and meiosis.","authors":"Martin Anger","doi":"10.1371/journal.pbio.3003206","DOIUrl":"10.1371/journal.pbio.3003206","url":null,"abstract":"<p><p>Mammalian oocytes are prone to chromosome segregation errors, which frequently lead into aneuploidy and pregnancy loss. A new study in PLOS Biology addresses the role of the Mad2/SGO2 complex in the control of separase activity in these cells during meiosis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003206"},"PeriodicalIF":9.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310688","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":"Understanding human brain function in real-world environments.","authors":"Feng Zhou, Benjamin Becker","doi":"10.1371/journal.pbio.3003210","DOIUrl":"10.1371/journal.pbio.3003210","url":null,"abstract":"<p><p>Functional MRI is invaluable in understanding brain function, but findings are often of limited real-world relevance. Neuroimaging in more naturalistic environments could reveal crucial insights into how the brain processes cognition, emotional experiences, and social interactions in daily life.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003210"},"PeriodicalIF":9.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310690","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":"EZH2 mutations increase the heterogeneity of chromatin states in lymphoma.","authors":"Daniel Holoch, Raphaël Margueron","doi":"10.1371/journal.pbio.3003211","DOIUrl":"10.1371/journal.pbio.3003211","url":null,"abstract":"<p><p>A recent study in PLoS Biology used simultaneous measurements of histone modifications in single cells to reveal that EZH2 gain-of-function mutations profoundly reprogram chromatin states in B-cell lymphoma, while also increasing their cell-cell heterogeneity.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 6","pages":"e3003211"},"PeriodicalIF":9.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289706","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}