eLife最新文献

{"title":"Decoding protein phosphorylation during oocyte meiotic divisions using phosphoproteomics.","authors":"Leonid Peshkin, Enrico Maria Daldello, Elizabeth S Van Itallie, Matthew Sonnett, Johannes Kreuzer, Wilhelm Haas, Marc W Kirschner, Catherine Jessus","doi":"10.7554/eLife.104255","DOIUrl":"10.7554/eLife.104255","url":null,"abstract":"<p><p>Oocyte meiotic divisions represent a critical process in sexual reproduction, as a diploid non-dividing oocyte is transformed into a haploid fertilizable egg, as a prelude for the subsequent embryonic divisions and differentiation. Although cell differentiation and proliferation are governed by transcription, oocyte maturation and early embryonic divisions depend entirely on changes in protein abundance and post-translational modifications. Here, we analyze the abundance and phosphorylation of proteins during <i>Xenopus</i> oocyte meiotic maturation. We reveal significant shifts in protein stability, related to spindle assembly, DNA replication, and RNA-binding. Our analysis pinpoints broad changes in phosphorylation correlating with key cytological meiotic milestones, noteworthy changes in membrane trafficking, nuclear envelope disassembly, and modifications in microtubule dynamics. Additionally, specific phosphorylation events target regulators of protein translation, Cdk1 and the Mos/MAPK pathway, thereby providing insight into the dynamics of Cdk1 activity, as related to the meiotic cell cycle. This study sheds light on the orchestration of protein dynamics and phosphorylation events during oocyte meiotic divisions, providing a rich resource for understanding the molecular pathways orchestrating meiotic progression in the frog, and most likely applicable to other vertebrate species.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648857","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":"Integration of parallel pathways for flight control in a hawkmoth reflects prevalence and relevance of natural visual cues.","authors":"Ronja Bigge, Rebecca Grittner, Anna Lisa Stöckl","doi":"10.7554/eLife.104118","DOIUrl":"10.7554/eLife.104118","url":null,"abstract":"<p><p>An animal's behaviour is the result of multiple neural pathways acting in parallel, receiving information across and within sensory modalities at the same time. How these pathways are integrated, particularly when their individual outputs are in conflict, is key to understanding complex natural behaviours. We investigated this question in the visually guided flight of the hummingbird hawkmoth <i>Macroglossum stellatarum</i>. These insects were recently shown to partition their visual field, using ventrolateral optic flow cues to guide their flight like most insects, while the same stimuli in the dorsal visual field evoke a novel directional response. Using behavioural experiments which set the two pathways into conflict, we tested whether and how the ventrolateral and dorsal pathway integrate to guide hawkmoth flight. Combined with environmental imaging, we demonstrate that the partitioning of the visual field followed the prevalence of visual cues in the hawkmoths' natural habitats, while the integration hierarchy of the two pathways matched the relevance of these cues for the animals' flight safety, rather than their magnitude in the experimental setup or in natural habitats. These results provide new mechanistic insights into the vision-based flight control of insects and link these to their natural context. We anticipate our findings to be the starting point for comparative investigations into parallel pathways for flight guidance in insects from differently structured natural habitats.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648861","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":"POMC neurons control fertility through differential signaling of MC4R in kisspeptin neurons.","authors":"Rajae Talbi, Todd L Stincic, Kaitlin Ferrari, Choi Ji Hae, Karol Walec, Elizabeth Medve, Achi Gerutshang, Silvia Leon, Elizabeth A McCarthy, Oline K Rønnekleiv, Martin J Kelly, Victor M Navarro","doi":"10.7554/eLife.100722","DOIUrl":"10.7554/eLife.100722","url":null,"abstract":"<p><p>Inactivating mutations in the melanocortin 4 receptor (<i>MC4R</i>) gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of Mc4r KO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown. Kiss1 neurons directly stimulate gonadotropin-releasing hormone (GnRH) release through two distinct populations: the Kiss1^ARH neurons, controlling GnRH pulses, and the sexually dimorphic Kiss1^AVPV/PeN neurons controlling the preovulatory luteinizing hormone (LH) surge. Here, we show that <i>Mc4r</i> expressed in Kiss1 neurons regulates fertility in females. In vivo, deletion of <i>Mc4r</i> from Kiss1 neurons in female mice replicates the reproductive impairments of Mc4r KO mice without inducing obesity. Conversely, re-insertion of <i>Mc4r</i> in Kiss1 neurons of Mc4r null mice restores estrous cyclicity and LH pulsatility without reducing their obese phenotype. In vitro, we dissect the specific action of Mc4r on Kiss1^ARH versus Kiss1^AVPV/PeN neurons and show that Mc4r activation excites Kiss1^ARH neurons through direct synaptic actions. In contrast, Kiss1^AVPV/PeN neurons are normally inhibited by MC4R activation except under elevated estradiol levels, thus facilitating the activation of Kiss1^AVPV/PeN neurons to induce the LH surge driving ovulation in females. Our findings demonstrate that POMC^ARH neurons acting through MC4R directly regulate reproductive function in females by stimulating the 'pulse generator' activity of Kiss1^ARH neurons and restricting the activation of Kiss1^AVPV/PeN neurons to the time of the estradiol-dependent LH surge, and thus unveil a novel pathway of the metabolic regulation of fertility by the melanocortin system.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648858","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":"How plants pick their friends.","authors":"Estelle Grundy, Michael Udvardi","doi":"10.7554/eLife.108116","DOIUrl":"10.7554/eLife.108116","url":null,"abstract":"<p><p>A protein called RIN4 has a central role in helping legumes such as soybean and the bacteria rhizobia to develop a mutually beneficial relationship.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648860","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":"Physical constraints and biological regulations underlie universal osmoresponses.","authors":"Yiyang Ye, Qirun Wang, Jie Lin","doi":"10.7554/eLife.102858","DOIUrl":"10.7554/eLife.102858","url":null,"abstract":"<p><p>Microorganisms constantly transition between environments with dramatically different external osmolarities. However, theories of microbial osmoresponse integrating physical constraints and biological regulations are lacking. Here, we propose such a theory, utilizing the separation of timescales for passive responses and active regulations. We demonstrate that regulations of osmolyte production and cell-wall synthesis assist cells in coping with intracellular crowding effects and adapting to a broad range of external osmolarity. Furthermore, we predict a threshold value above which cells cannot grow, ubiquitous across bacteria and yeast. Intriguingly, the theory predicts a dramatic speedup of cell growth after an abrupt decrease in external osmolarity due to cell-wall synthesis regulation. Our theory rationalizes the unusually fast growth observed in fission yeast after an oscillatory osmotic perturbation, and the predicted growth rate peaks match quantitatively with experimental measurements. Our study reveals the physical basis of osmoresponse, yielding far-reaching implications for microbial physiology.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642115","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 myeloid cell-driven transdifferentiation of endothelial cells into pericytes promotes the restoration of BBB function and brain self-repair after stroke.","authors":"Tingbo Li, Ling Yang, Jiaqi Tu, Yufan Hao, Zhu Zhu, Yingjie Xiong, Qingzhu Gao, Lili Zhou, Guanglei Xie, Dongdong Zhang, Xuzhao Li, Yuxiao Jin, Yiyi Zhang, Bingrui Zhao, Nan Li, Xi Wang, Jie-Min Jia","doi":"10.7554/eLife.105593","DOIUrl":"10.7554/eLife.105593","url":null,"abstract":"<p><p>Ischemic stroke, one of the leading causes of death in the world, is accompanied by the dysfunction of the blood-brain barrier (BBB), which aggravates neuron damage. However, the mechanisms underlying the restoration of BBB in the chronic stage after stroke remain unclear. Here, pericyte pool alterations and their consequences for BBB integrity and brain recovery were analyzed in the C57BL/6 mice stroke model. Lineage tracing, RNA-seq, and immunofluorescence staining revealed endothelial cell (EC) transdifferentiation into pericytes (E-pericytes) in C57BL/6 mice after stroke. E-pericytes depletion by diphtheria toxin A (DTA) aggravated BBB leakage and exacerbated neurological deficits in the MCAO model. The myeloid cell-driven transdifferentiation of ECs into pericytes accelerated BBB restoration and brain self-repair after stroke via endothelial-mesenchymal transformation (EndoMT). Decreasing the number of E-pericytes by specific knockout of the <i>Tgfbr2</i> gene in ECs also aggravated BBB leakage and exacerbated neurological deficits. EC-specific overexpression of the <i>Tgfbr2</i> gene promoting E-pericytes transdifferentiation reduced BBB leakage and exerted neuroprotective effects. Deciphering the mechanism by which E-pericytes coordinate post-stroke recovery may reveal a novel therapeutic opportunity.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642120","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":"Heron, a Knowledge Graph editor for intuitive implementation of Python-based experimental pipelines.","authors":"George Dimitriadis, Ella Svahn, Andrew F MacAskill, Athena Akrami","doi":"10.7554/eLife.91915","DOIUrl":"10.7554/eLife.91915","url":null,"abstract":"<p><p>To realise a research project, experimenters face conflicting design and implementation choices across hardware and software. These include balancing ease of implementation - time, expertise, and resources - against future flexibility, the number of opaque (black box) components and reproducibility. To address this, we present Heron, a Python-based platform for constructing and running experimental and data analysis pipelines. Heron allows researchers to design experiments according to their own mental schemata, represented as a Knowledge Graph - a structure that mirrors the logical flow of an experiment. This approach speeds up implementation (and subsequent updates), while minimising black box components, increasing transparency and reproducibility. Heron supports the integration of software and hardware combinations that are otherwise too complex or costly, making it especially useful in experimental sciences with a large number of interconnected components such as robotics, neuroscience, behavioural sciences, physics, chemistry, and environmental sciences. Unlike visual-only tools, Heron combines full control (of instrument and software combinations) and flexibility with the ease of high-level programming and Graphical User Interfaces. It assumes intermediate Python proficiency and offers a clean, modular code base that encourages documentation and reuse. By removing inaccessible technical barriers, Heron enables researchers without formal engineering backgrounds to construct sophisticated, reliable and reproducible experimental setups - bridging the gap between scientific creativity and technical implementation.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642114","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":"Single neurons and networks in the mouse claustrum integrate input from widespread cortical sources.","authors":"Andrew M Shelton, David K Oliver, Ivan P Lazarte, Joachim S Grimstvedt, Ishaan Kapoor, Jake A Swann, Caitlin A Ashcroft, Simon N Williams, Niall Conway, Selma Tir, Amy Robinson, Stuart Peirson, Thomas Akam, Clifford G Kentros, Menno P Witter, Simon J B Butt, Adam Max Packer","doi":"10.7554/eLife.98002","DOIUrl":"10.7554/eLife.98002","url":null,"abstract":"<p><p>The claustrum is thought to be one of the most highly interconnected forebrain structures, but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons in <i>Mus musculus</i> to understand how the structure's unique convergence of input and divergence of output support binding information streams. We found that neurons in the claustrum communicate with each other across efferent projection-defined modules which were differentially innervated by sensory and frontal cortical areas. Individual claustrum neurons were responsive to inputs from more than one cortical region in a cell-type and projection-specific manner, particularly between areas of frontal cortex. In vivo imaging of claustrum axons revealed responses to both unimodal and multimodal sensory stimuli. Finally, chronic claustrum silencing specifically reduced animals' sensitivity to multimodal stimuli. These findings support the view that the claustrum is a fundamentally integrative structure, consolidating information from around the cortex and redistributing it following local computations.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642116","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":"Structure of human PIEZO1 and its slow-inactivating channelopathy mutants.","authors":"Yuanyue Shan, Xinyi Guo, Mengmeng Zhang, Meiyu Chen, Ying Li, Mingfeng Zhang, Duanqing Pei","doi":"10.7554/eLife.101923","DOIUrl":"10.7554/eLife.101923","url":null,"abstract":"<p><p>PIEZO channels transmit mechanical force signals to cells, allowing them to make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated in mechanopathologies but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) and its slow-inactivating channelopathy mutants with or without its auxiliary subunit MDFIC. Our results suggest that hPIEZO1 has a more flattened and extended architecture than curved mouse PIEZO1 (mPIEZO1). The multi-lipidated MDFIC subunits insert laterally into the hPIEZO1 pore module like mPIEZO1, resulting in a more curved and extended state. Interestingly, the high-resolution structures suggest that the pore lipids, which directly seal the central hydrophobic pore, may be involved in the rapid inactivation of hPIEZO1. While the severe hereditary erythrocytosis mutant R2456H significantly slows down the inactivation of hPIEZO1, the hPIEZO1-R2456H-MDFIC complex shows a more curved and contracted structure with an inner helix twist due to the broken link between the pore lipid and R2456H. These results suggest that the pore lipids may be involved in the mechanopathological rapid inactivation mechanism of PIEZO channels.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642117","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":"Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc.","authors":"Changli Zhang, Martha Elena Diaz-Hernandez, Takanori Fukunaga, Sreekala Shenoy, Sangwook Tim Yoon, Lisbet Haglund, Hicham Drissi","doi":"10.7554/eLife.103073","DOIUrl":"10.7554/eLife.103073","url":null,"abstract":"<p><p>Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. While previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptotic and pro-anabolic effects, its impact on IVD cell senescence remains elusive. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for 5 d. Transcriptome profiling by mRNA sequencing revealed that NP and AF cells responded to the treatment in similar yet distinct ways. The effects of PDGF-AB and BB on human IVD cells were comparable. Specifically, rhPDGF-AB/BB treatment downregulated genes related to neurogenesis and mechanical stimulus response in AF cells, while in NP cells, metabolic pathways were predominantly suppressed. In both NP and AF cells, rhPDGF-AB/BB treatment upregulated genes involved in cell cycle regulation and response to reduced oxygen levels, while downregulating genes related to senescence-associated phenotype, including oxidative stress, reactive oxygen species (ROS), and mitochondria dysfunction. Network analysis revealed that PDGFRA and IL6 were the top hub genes in treated NP cells. Furthermore, in irradiation-induced senescent NP cells, PDGFRA gene expression was significantly reduced compared to non-irradiated cells. However, rhPDGF-AB/BB treatment increased PDGFRA expression and mitigated the senescence progression through increased cell population in the S phase, reduced SA-β-Gal activity, and decreased expression of senescence-related regulators. Our findings reveal a novel anti-senescence role of PDGF in the IVD, making it a promising potential candidate to delay aging-induced IVD degeneration.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642118","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}