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RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer. RNA 剪接接头景观揭示了人类癌症中丰富的肿瘤特异性转录本。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-23 DOI: 10.1016/j.celrep.2024.114893
Qin Li, Ziteng Li, Bing Chen, Jingjing Zhao, Hongwu Yu, Jia Hu, Hongyan Lai, Hena Zhang, Yan Li, Zhiqiang Meng, Zhixiang Hu, Shenglin Huang
{"title":"RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer.","authors":"Qin Li, Ziteng Li, Bing Chen, Jingjing Zhao, Hongwu Yu, Jia Hu, Hongyan Lai, Hena Zhang, Yan Li, Zhiqiang Meng, Zhixiang Hu, Shenglin Huang","doi":"10.1016/j.celrep.2024.114893","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114893","url":null,"abstract":"<p><p>RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114893"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496010","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
Persistent bone marrow hemozoin accumulation confers a survival advantage against bacterial infection via cell-intrinsic Myd88 signaling. 骨髓造血素的持续积累通过细胞内Myd88信号传导赋予了对抗细菌感染的生存优势。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-10 DOI: 10.1016/j.celrep.2024.114850
Yanhui Zhu, Qingxiang Gao, Jia Zhang, Yu Cheng, Shuzhen Yang, Ren Xu, Jing Yuan, Boris Novakovic, Mihai G Netea, Shih-Chin Cheng
{"title":"Persistent bone marrow hemozoin accumulation confers a survival advantage against bacterial infection via cell-intrinsic Myd88 signaling.","authors":"Yanhui Zhu, Qingxiang Gao, Jia Zhang, Yu Cheng, Shuzhen Yang, Ren Xu, Jing Yuan, Boris Novakovic, Mihai G Netea, Shih-Chin Cheng","doi":"10.1016/j.celrep.2024.114850","DOIUrl":"10.1016/j.celrep.2024.114850","url":null,"abstract":"<p><p>Malaria remains a global health challenge, affecting millions annually. Hemozoin (Hz) deposition in the bone marrow disrupts hematopoiesis and modulates immune responses, but the mechanisms are not fully understood. Here, we show that persistent hemozoin deposition induces a sustained bias toward myelopoiesis, increasing peripheral myeloid cell numbers. Hz drives this process through a cell-intrinsic, MyD88-dependent pathway, enhancing chromatin accessibility of transcription factors such as Runx1 and Etv6 in granulocyte-macrophage progenitors. These findings are confirmed by intraosseous Hz injections and bone marrow chimeras. Single-cell RNA sequencing reveals increased reactive oxygen species production in monocytes from malaria-recovered mice, correlating with enhanced bactericidal capacity. This highlights an alternative aspect of post-malarial immunity and extends our understanding of trained immunity, suggesting that pathogen by-products like Hz can induce innate immune memory. These results offer insights into therapeutic strategies that harness trained immunity to combat infectious diseases.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114850"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406181","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
Comprehensive mapping of sensory and sympathetic innervation of the developing kidney. 全面绘制发育中肾脏的感觉和交感神经支配图。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-15 DOI: 10.1016/j.celrep.2024.114860
Pierre-Emmanuel Y N'Guetta, Sarah R McLarnon, Adrien Tassou, Matan Geron, Sepenta Shirvan, Rose Z Hill, Grégory Scherrer, Lori L O'Brien
{"title":"Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.","authors":"Pierre-Emmanuel Y N'Guetta, Sarah R McLarnon, Adrien Tassou, Matan Geron, Sepenta Shirvan, Rose Z Hill, Grégory Scherrer, Lori L O'Brien","doi":"10.1016/j.celrep.2024.114860","DOIUrl":"10.1016/j.celrep.2024.114860","url":null,"abstract":"<p><p>The kidneys act as finely tuned sensors to maintain physiological homeostasis. Both sympathetic and sensory nerves modulate kidney function through precise neural control. However, how the kidneys are innervated during development to support function remains elusive. Using light-sheet and confocal microscopy, we generated anatomical maps of kidney innervation across development. Kidney innervation commences on embryonic day 13.5 (E13.5) as network growth aligns with arterial differentiation. Fibers are synapsin I<sup>+</sup>, highlighting ongoing axonogenesis and potential signaling crosstalk. By E17.5, axons associate with nephrons, and the network continues to expand postnatally. CGRP<sup>+</sup>, substance P<sup>+</sup>, TRPV1<sup>+</sup>, and PIEZO2<sup>+</sup> sensory fibers and TH<sup>+</sup> sympathetic fibers innervate the developing kidney. TH<sup>+</sup> and PIEZO2<sup>+</sup> axons similarly innervate the human kidney, following the arterial tree to reach targets. Retrograde tracing revealed the primary dorsal root ganglia, T10-L2, from which sensory neurons project to the kidneys. Together, our findings elucidate the temporality and neuronal diversity of kidney innervation.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114860"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459138","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
Developmental refinement of the active zone nanotopography and axon wiring at the somatosensory thalamus. 体感丘脑活动区纳米图谱和轴突线路的发育完善
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-24 DOI: 10.1016/j.celrep.2024.114770
Mitsuharu Midorikawa, Hirokazu Sakamoto, Yukihiro Nakamura, Kenzo Hirose, Mariko Miyata
{"title":"Developmental refinement of the active zone nanotopography and axon wiring at the somatosensory thalamus.","authors":"Mitsuharu Midorikawa, Hirokazu Sakamoto, Yukihiro Nakamura, Kenzo Hirose, Mariko Miyata","doi":"10.1016/j.celrep.2024.114770","DOIUrl":"10.1016/j.celrep.2024.114770","url":null,"abstract":"<p><p>Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114770"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342474","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
Position-independent functional refinement within the vagus motor topographic map. 迷走神经运动地形图中与位置无关的功能细化。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-25 DOI: 10.1016/j.celrep.2024.114740
Takuya Kaneko, Jonathan Boulanger-Weill, Adam J Isabella, Cecilia B Moens
{"title":"Position-independent functional refinement within the vagus motor topographic map.","authors":"Takuya Kaneko, Jonathan Boulanger-Weill, Adam J Isabella, Cecilia B Moens","doi":"10.1016/j.celrep.2024.114740","DOIUrl":"10.1016/j.celrep.2024.114740","url":null,"abstract":"<p><p>Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here, we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity among intermingled motor populations.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114740"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342484","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
Spindle oscillations emerge at the critical state of electrically coupled networks in the thalamic reticular nucleus. 丘脑网状核电耦合网络的临界状态出现纺锤体振荡。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-01 DOI: 10.1016/j.celrep.2024.114790
Shangyang Li, Chaoming Wang, Si Wu
{"title":"Spindle oscillations emerge at the critical state of electrically coupled networks in the thalamic reticular nucleus.","authors":"Shangyang Li, Chaoming Wang, Si Wu","doi":"10.1016/j.celrep.2024.114790","DOIUrl":"10.1016/j.celrep.2024.114790","url":null,"abstract":"<p><p>Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7-15 Hz. Experiments have shown that in the adult brain, electrical synapses, rather than chemical synapses, dominate between TRN neurons, suggesting that the traditional view of spindle generation via chemical synapses may need reconsideration. Based on known experimental data, we develop a computational model of the TRN network, where heterogeneous neurons are connected by electrical synapses. The model shows that the interplay between synchronizing electrical synapses and desynchronizing heterogeneity leads to multiple synchronized clusters with slightly different oscillation frequencies whose summed-up activity produces spindle oscillation as seen in local field potentials. Our results suggest that during spindle oscillation, the network operates at the critical state, which is known for facilitating efficient information processing. This study provides insights into the underlying mechanism of spindle oscillation and its functional significance.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114790"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364574","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
Nucleoporin Nsp1 surveils the phase state of FG-Nups. 核蛋白 Nsp1 监控 FG-Nups 的相态。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-01 DOI: 10.1016/j.celrep.2024.114793
Tegan A Otto, Tessa Bergsma, Maurice Dekker, Sara N Mouton, Paola Gallardo, Justina C Wolters, Anton Steen, Patrick R Onck, Liesbeth M Veenhoff
{"title":"Nucleoporin Nsp1 surveils the phase state of FG-Nups.","authors":"Tegan A Otto, Tessa Bergsma, Maurice Dekker, Sara N Mouton, Paola Gallardo, Justina C Wolters, Anton Steen, Patrick R Onck, Liesbeth M Veenhoff","doi":"10.1016/j.celrep.2024.114793","DOIUrl":"10.1016/j.celrep.2024.114793","url":null,"abstract":"<p><p>Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup condensates, promoting a liquid-like state. Nsp1's presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC defects and a general decline in protein quality control that quantitatively mimics aging phenotypes. These phenotypes can be rescued by a cytosolic form of Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114793"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364572","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
ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA. ADA2 是一种作用于 DNA 的溶酶体脱氧腺苷脱氨酶，参与调节 TLR9 介导的 DNA 免疫感应。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 DOI: 10.1016/j.celrep.2024.114899
Ole Kristian Greiner-Tollersrud, Máté Krausz, Vincent Boehler, Aikaterini Polyzou, Maximilian Seidl, Ambra Spahiu, Zeinab Abdullah, Katarzyna Andryka-Cegielski, Felix Immunuel Dominick, Katrin Huebscher, Andreas Goschin, Cristian R Smulski, Eirini Trompouki, Regina Link, Hilmar Ebersbach, Honnappa Srinivas, Martine Marchant, Georgios Sogkas, Dieter Staab, Cathrine Vågbø, Danilo Guerini, Sebastian Baasch, Eicke Latz, Gunther Hartmann, Philippe Henneke, Roger Geiger, Xiao P Peng, Bodo Grimbacher, Eva Bartok, Ingrun Alseth, Max Warncke, Michele Proietti
{"title":"ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA.","authors":"Ole Kristian Greiner-Tollersrud, Máté Krausz, Vincent Boehler, Aikaterini Polyzou, Maximilian Seidl, Ambra Spahiu, Zeinab Abdullah, Katarzyna Andryka-Cegielski, Felix Immunuel Dominick, Katrin Huebscher, Andreas Goschin, Cristian R Smulski, Eirini Trompouki, Regina Link, Hilmar Ebersbach, Honnappa Srinivas, Martine Marchant, Georgios Sogkas, Dieter Staab, Cathrine Vågbø, Danilo Guerini, Sebastian Baasch, Eicke Latz, Gunther Hartmann, Philippe Henneke, Roger Geiger, Xiao P Peng, Bodo Grimbacher, Eva Bartok, Ingrun Alseth, Max Warncke, Michele Proietti","doi":"10.1016/j.celrep.2024.114899","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114899","url":null,"abstract":"<p><p>Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114899"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496001","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
HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma. 通过ICP0介导的METTL14抑制HSV-1诱导的N6-甲基腺苷重编程可增强胶质瘤的溶瘤活性。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-25 DOI: 10.1016/j.celrep.2024.114756
Yuling Chen, Shasha Bian, Jiamei Zhang, Yuxuan Luan, Bowen Yin, Weiwei Dai, Hanlin Wang, Xi Chen, Yan Dong, Yiheng Cai, Ruitao Dong, Liubing Yu, Minfeng Shu
{"title":"HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma.","authors":"Yuling Chen, Shasha Bian, Jiamei Zhang, Yuxuan Luan, Bowen Yin, Weiwei Dai, Hanlin Wang, Xi Chen, Yan Dong, Yiheng Cai, Ruitao Dong, Liubing Yu, Minfeng Shu","doi":"10.1016/j.celrep.2024.114756","DOIUrl":"10.1016/j.celrep.2024.114756","url":null,"abstract":"<p><p>Upon infection with herpes simplex virus 1 (HSV-1), the virus deploys multiple strategies to evade the host's innate immune response. However, the mechanisms governing this phenomenon remain elusive. Here, we find that HSV-1 leads to a decrease in overall m6A levels by selectively reducing METTL14 protein during early infection in glioma cells. Specifically, the HSV-1-encoded immediate-early protein ICP0 interacts with METTL14 within ND10 bodies and serves as an E3 ubiquitin protein ligase, targeting and ubiquitinating METTL14 at the lysine 156 and 162 sites. Subsequently, METTL14 undergoes proteasomal degradation. Furthermore, METTL14 stabilizes ISG15 mRNA mediated by IGF2BP3 to promote antiviral effects. Notably, METTL14 suppression significantly enhances the anti-tumor effect of oncolytic HSV-1 (oHSV-1) in mice bearing glioma xenografts. Collectively, these findings establish that ICP0-guided m6A modification controls the antiviral immune response and suggest that targeting METTL14/ISG15 represents a potential strategy to enhance the oncolytic activity of oHSV-1 in glioma treatment.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114756"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342478","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
Neuronal exosomes transport an miRISC cargo to preserve stem cell integrity during energy stress. 神经元外泌体运输miRISC货物，以在能量应激时保持干细胞的完整性。
IF 7.5 1区 生物学
Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-10 DOI: 10.1016/j.celrep.2024.114851
Christopher Wong, Elena M Jurczak, Richard Roy
{"title":"Neuronal exosomes transport an miRISC cargo to preserve stem cell integrity during energy stress.","authors":"Christopher Wong, Elena M Jurczak, Richard Roy","doi":"10.1016/j.celrep.2024.114851","DOIUrl":"10.1016/j.celrep.2024.114851","url":null,"abstract":"<p><p>During periods of nutrient scarcity, many animals undergo germline quiescence to preserve reproductive capacity, and neurons are often necessary for this adaptation. We show here that starvation causes the release of neuronal microRNA (miRNA)/Argonaute-loaded exosomes following AMP kinase-regulated trafficking changes within serotonergic neurons. This neuron-to-germline communication is independent of classical neurotransmission but instead relies on endosome-derived vesicles that carry a pro-quiescent small RNA cargo to modify germline gene expression. Using an miRNA activity sensor, we show that neuronally expressed miRNAs can extinguish the expression of germline mRNA targets in an exosome-dependent manner. Our findings demonstrate how an adaptive neuronal response can change gene expression at a distance by redirecting intracellular trafficking to release neuronal exosomes with specific miRNA cargoes capable of tracking to their appropriate destinations.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114851"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406180","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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