Pub Date : 2024-08-31DOI: 10.1016/j.celrep.2024.114702
Zheyang Sam Zheng, Roman Huszár, Thomas Hainmueller, Marlene Bartos, Alex H Williams, György Buzsáki
Representation of the environment by hippocampal populations is known to drift even within a familiar environment, which could reflect gradual changes in single-cell activity or result from averaging across discrete switches of single neurons. Disambiguating these possibilities is crucial, as they each imply distinct mechanisms. Leveraging change point detection and model comparison, we find that CA1 population vectors decorrelate gradually within a session. In contrast, individual neurons exhibit predominantly step-like emergence and disappearance of place fields or sustained changes in within-field firing. The changes are not restricted to particular parts of the maze or trials and do not require apparent behavioral changes. The same place fields emerge, disappear, and reappear across days, suggesting that the hippocampus reuses pre-existing assemblies, rather than forming new fields de novo. Our results suggest an internally driven perpetual step-like reorganization of the neuronal assemblies.
{"title":"Perpetual step-like restructuring of hippocampal circuit dynamics.","authors":"Zheyang Sam Zheng, Roman Huszár, Thomas Hainmueller, Marlene Bartos, Alex H Williams, György Buzsáki","doi":"10.1016/j.celrep.2024.114702","DOIUrl":"10.1016/j.celrep.2024.114702","url":null,"abstract":"<p><p>Representation of the environment by hippocampal populations is known to drift even within a familiar environment, which could reflect gradual changes in single-cell activity or result from averaging across discrete switches of single neurons. Disambiguating these possibilities is crucial, as they each imply distinct mechanisms. Leveraging change point detection and model comparison, we find that CA1 population vectors decorrelate gradually within a session. In contrast, individual neurons exhibit predominantly step-like emergence and disappearance of place fields or sustained changes in within-field firing. The changes are not restricted to particular parts of the maze or trials and do not require apparent behavioral changes. The same place fields emerge, disappear, and reappear across days, suggesting that the hippocampus reuses pre-existing assemblies, rather than forming new fields de novo. Our results suggest an internally driven perpetual step-like reorganization of the neuronal assemblies.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104765","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}
Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.
{"title":"Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment.","authors":"Zhiwen Luo, Jie Mei, Xianwen Wang, Ruixin Wang, Zhao He, Yifat Geffen, Xiaomeng Sun, Xingyu Zhang, Junying Xu, Renwen Wan, Xinting Feng, Chunmeng Jiao, Xiaoping Su, Junming Sun, Shiyi Chen, Jiwu Chen, Wenjun Mao, Yunlong Yang, Yaying Sun","doi":"10.1016/j.celrep.2024.114697","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114697","url":null,"abstract":"<p><p>Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104773","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}
Pub Date : 2024-08-30DOI: 10.1016/j.celrep.2024.114671
Jiawen Yang, Peiyu Shi, Yiheng Li, Yachao Zuo, Yage Nie, Tao Xu, Dongjie Peng, Ziyang An, Tingting Huang, Jingyi Zhang, Weixing Zhang, Yicong Xu, Zhongjie Tang, Anan Li, Jin Xu
Recent discoveries have revealed remarkable complexity within olfactory sensory neurons (OSNs), including the existence of two OSN populations based on the expression of Cd36. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive. Here, we show the preferential expression of 79 olfactory receptors in Cd36+ OSNs and the anterior projection characteristics of Cd36+ OSNs, indicating the non-randomness of Cd36 expression. The integrated analysis of single-cell RNA sequencing (scRNA-seq) and scATAC-seq reveals that the differences in Cd36+/- OSNs occur at the immature OSN stage, with Mef2a and Hdac9 being important regulators of developmental divergence. We hypothesize that the absence of Hdac9 may affect the activation of Mef2a, leading to the up-regulation of Mef2a target genes, including teashirt zinc finger family member 1 (Tshz1), in the Cd36+ OSN lineage. We validate that Tshz1 directly promotes Cd36 expression through enhancer bindings. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system.
{"title":"Regulatory mechanisms orchestrating cellular diversity of Cd36+ olfactory sensory neurons revealed by scRNA-seq and scATAC-seq analysis.","authors":"Jiawen Yang, Peiyu Shi, Yiheng Li, Yachao Zuo, Yage Nie, Tao Xu, Dongjie Peng, Ziyang An, Tingting Huang, Jingyi Zhang, Weixing Zhang, Yicong Xu, Zhongjie Tang, Anan Li, Jin Xu","doi":"10.1016/j.celrep.2024.114671","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114671","url":null,"abstract":"<p><p>Recent discoveries have revealed remarkable complexity within olfactory sensory neurons (OSNs), including the existence of two OSN populations based on the expression of Cd36. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive. Here, we show the preferential expression of 79 olfactory receptors in Cd36+ OSNs and the anterior projection characteristics of Cd36+ OSNs, indicating the non-randomness of Cd36 expression. The integrated analysis of single-cell RNA sequencing (scRNA-seq) and scATAC-seq reveals that the differences in Cd36+/- OSNs occur at the immature OSN stage, with Mef2a and Hdac9 being important regulators of developmental divergence. We hypothesize that the absence of Hdac9 may affect the activation of Mef2a, leading to the up-regulation of Mef2a target genes, including teashirt zinc finger family member 1 (Tshz1), in the Cd36+ OSN lineage. We validate that Tshz1 directly promotes Cd36 expression through enhancer bindings. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104766","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}
During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-TTSM cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (TPEX) cells and further replenishes tumor-specific CD8+ T cells residing in the tumor microenvironment (TME). However, how TTSM cells are maintained in TdLN is largely unknown. Here, we show that the transcription regulator ID3 (inhibitor of DNA binding 3) is highly expressed by TTSM cells compared with other CD8+ T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of TTSM and TPEX cells, resulting in decreased tumor-infiltrating CD8+ T cells and impaired tumor control. Consistent with this, overexpression of ID3 in CD8+ T cells increases the TTSM cell population and enhances the anti-tumor immune response.
在肿瘤发生过程中,最近发现的引流淋巴结中的肿瘤特异性记忆 T 细胞(TdLN-TTSM 细胞)在肿瘤抑制过程中发挥了关键作用,这种抑制产生了原代衰竭 T(TPEX)细胞,并进一步补充了驻留在肿瘤微环境(TME)中的肿瘤特异性 CD8+ T 细胞。然而,TTSM 细胞是如何在 TdLN 中维持的目前还不清楚。在这里,我们发现与其他 CD8+ T 细胞亚群相比,TTSM 细胞高度表达转录调节因子 ID3(DNA 结合抑制因子 3)。ID3 的缺乏会明显干扰 TTSM 和 TPEX 细胞的维持,导致肿瘤浸润性 CD8+ T 细胞减少,肿瘤控制能力受损。与此相一致的是,在 CD8+ T 细胞中过表达 ID3 会增加 TTSM 细胞数量并增强抗肿瘤免疫反应。
{"title":"The transcription regulator ID3 maintains tumor-specific memory CD8<sup>+</sup> T cells in draining lymph nodes during tumorigenesis.","authors":"Ling Ran, Zhengliang Yue, Mengqu Ran, Qiao Liu, Xingxing Su, Lisha Wang, Shuqiong Wen, Luming Xu, Shun Lei, Zhanpeng Ou, Jianjun Hu, Yan Zhang, Chenxi Qin, Yuzhu Wang, Qinyi He, Yezi Chen, Wen Liu, Lilin Ye, Qizhao Huang, Lifan Xu","doi":"10.1016/j.celrep.2024.114690","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114690","url":null,"abstract":"<p><p>During tumorigenesis, the recently identified tumor-specific memory T cells in draining lymph nodes (TdLN-T<sub>TSM</sub> cells) play a pivotal role in tumor repression that gives rise to progenitor exhausted T (T<sub>PEX</sub>) cells and further replenishes tumor-specific CD8<sup>+</sup> T cells residing in the tumor microenvironment (TME). However, how T<sub>TSM</sub> cells are maintained in TdLN is largely unknown. Here, we show that the transcription regulator ID3 (inhibitor of DNA binding 3) is highly expressed by T<sub>TSM</sub> cells compared with other CD8<sup>+</sup> T cell subsets. The deficiency of ID3 significantly interrupts the maintenance of T<sub>TSM</sub> and T<sub>PEX</sub> cells, resulting in decreased tumor-infiltrating CD8<sup>+</sup> T cells and impaired tumor control. Consistent with this, overexpression of ID3 in CD8<sup>+</sup> T cells increases the T<sub>TSM</sub> cell population and enhances the anti-tumor immune response.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104770","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}
Histone lysine lactylation (Kla) is a post-translational modification, and its role in tumor immune escape remains unclear. Here, we find that increased histone lactylation is associated with poor response to immunotherapy in head and neck squamous cell carcinoma (HNSCC). H3K9la is identified as a specific modification site in HNSCC. Using cleavage under targets and tagmentation analyses, interleukin-11 (IL-11) is identified as a downstream regulatory gene of H3K9la. IL-11 transcriptionally activates immune checkpoint genes through JAK2/STAT3 signaling in CD8+ T cells. Additionally, IL-11 overexpression promotes tumor progression and CD8+ T cell dysfunction in vivo. Moreover, IL11 knockdown reverses lactate-induced CD8+ T cell exhaustion, and cholesterol-modified siIL11 restores CD8+ T cell killing activity and enhances immunotherapy efficacy. Clinically, H3K9la positively correlates with IL-11 expression and unfavorable immunotherapy responses in patients. This study reveals the crucial role of histone lactylation in immune escape, providing insights into immunotherapy strategies for HNSCC.
{"title":"H3K9 lactylation in malignant cells facilitates CD8<sup>+</sup> T cell dysfunction and poor immunotherapy response.","authors":"Ruijie Wang, Chuwen Li, Zhongyi Cheng, Mingyu Li, Jianbo Shi, Zhiyuan Zhang, Shufang Jin, Hailong Ma","doi":"10.1016/j.celrep.2024.114686","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114686","url":null,"abstract":"<p><p>Histone lysine lactylation (Kla) is a post-translational modification, and its role in tumor immune escape remains unclear. Here, we find that increased histone lactylation is associated with poor response to immunotherapy in head and neck squamous cell carcinoma (HNSCC). H3K9la is identified as a specific modification site in HNSCC. Using cleavage under targets and tagmentation analyses, interleukin-11 (IL-11) is identified as a downstream regulatory gene of H3K9la. IL-11 transcriptionally activates immune checkpoint genes through JAK2/STAT3 signaling in CD8<sup>+</sup> T cells. Additionally, IL-11 overexpression promotes tumor progression and CD8<sup>+</sup> T cell dysfunction in vivo. Moreover, IL11 knockdown reverses lactate-induced CD8<sup>+</sup> T cell exhaustion, and cholesterol-modified siIL11 restores CD8<sup>+</sup> T cell killing activity and enhances immunotherapy efficacy. Clinically, H3K9la positively correlates with IL-11 expression and unfavorable immunotherapy responses in patients. This study reveals the crucial role of histone lactylation in immune escape, providing insights into immunotherapy strategies for HNSCC.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104760","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}
Pub Date : 2024-08-30DOI: 10.1016/j.celrep.2024.114652
Xianghe Qiao, Nengwen Huang, Wanrong Meng, Yunkun Liu, Jinjin Li, Chunjie Li, Wenxuan Wang, Yi Lai, Yongjiang Zhao, Zhongkai Ma, Jingya Li, Xuan Zhang, Zhijie Weng, Chenzhou Wu, Longjiang Li, Bo Li
Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion "selectively" revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.
{"title":"Beyond mitochondrial transfer, cell fusion rescues metabolic dysfunction and boosts malignancy in adenoid cystic carcinoma.","authors":"Xianghe Qiao, Nengwen Huang, Wanrong Meng, Yunkun Liu, Jinjin Li, Chunjie Li, Wenxuan Wang, Yi Lai, Yongjiang Zhao, Zhongkai Ma, Jingya Li, Xuan Zhang, Zhijie Weng, Chenzhou Wu, Longjiang Li, Bo Li","doi":"10.1016/j.celrep.2024.114652","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114652","url":null,"abstract":"<p><p>Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion \"selectively\" revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104754","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}
Pub Date : 2024-08-29DOI: 10.1016/j.celrep.2024.114653
Yinyin Ma, Anton Kan, David R Johnson
Surface-associated microbial systems are hotspots for the spread of plasmid-encoded antibiotic resistance, but how surface association affects plasmid transfer and proliferation remains unclear. Surface association enables prolonged spatial proximities between different populations, which promotes plasmid transfer between them. However, surface association also fosters strong metabolic interactions between different populations, which can direct their spatial self-organization with consequences for plasmid transfer and proliferation. Here, we hypothesize that metabolic interactions direct the spatial self-organization of different populations and, in turn, regulate the spread of plasmid-encoded antibiotic resistance. We show that resource competition causes populations to spatially segregate, which represses plasmid transfer. In contrast, resource cross-feeding causes populations to spatially intermix, which promotes plasmid transfer. We further show that the spatial positionings that emerge from metabolic interactions determine the proliferation of plasmid recipients. Our results demonstrate that metabolic interactions are important regulators of both the transfer and proliferation of plasmid-encoded antibiotic resistance.
{"title":"Metabolic interactions control the transfer and spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth.","authors":"Yinyin Ma, Anton Kan, David R Johnson","doi":"10.1016/j.celrep.2024.114653","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114653","url":null,"abstract":"<p><p>Surface-associated microbial systems are hotspots for the spread of plasmid-encoded antibiotic resistance, but how surface association affects plasmid transfer and proliferation remains unclear. Surface association enables prolonged spatial proximities between different populations, which promotes plasmid transfer between them. However, surface association also fosters strong metabolic interactions between different populations, which can direct their spatial self-organization with consequences for plasmid transfer and proliferation. Here, we hypothesize that metabolic interactions direct the spatial self-organization of different populations and, in turn, regulate the spread of plasmid-encoded antibiotic resistance. We show that resource competition causes populations to spatially segregate, which represses plasmid transfer. In contrast, resource cross-feeding causes populations to spatially intermix, which promotes plasmid transfer. We further show that the spatial positionings that emerge from metabolic interactions determine the proliferation of plasmid recipients. Our results demonstrate that metabolic interactions are important regulators of both the transfer and proliferation of plasmid-encoded antibiotic resistance.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104762","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}
Pub Date : 2024-08-29DOI: 10.1016/j.celrep.2024.114665
Linghua Zhang, Maximilian Nagel, William P Olson, Alexander T Chesler, Daniel H O'Connor
The neural basis of tongue mechanosensation remains largely mysterious despite the tongue's high tactile acuity, sensitivity, and relevance to ethologically important functions. We studied terminal morphologies and tactile responses of lingual afferents from the trigeminal ganglion. Fungiform papillae, the taste-bud-holding structures in the tongue, were convergently innervated by multiple Piezo2+ trigeminal afferents, whereas single trigeminal afferents branched into multiple adjacent filiform papillae. In vivo single-unit recordings from the trigeminal ganglion revealed lingual low-threshold mechanoreceptors (LTMRs) with distinct tactile properties ranging from intermediately adapting (IA) to rapidly adapting (RA). The receptive fields of these LTMRs were mostly less than 0.1 mm2 and concentrated at the tip of the tongue, resembling the distribution of fungiform papillae. Our results indicate that fungiform papillae are mechanosensory structures and suggest a simple model that links functional and anatomical properties of tactile sensory neurons in the tongue.
{"title":"Trigeminal innervation and tactile responses in mouse tongue.","authors":"Linghua Zhang, Maximilian Nagel, William P Olson, Alexander T Chesler, Daniel H O'Connor","doi":"10.1016/j.celrep.2024.114665","DOIUrl":"10.1016/j.celrep.2024.114665","url":null,"abstract":"<p><p>The neural basis of tongue mechanosensation remains largely mysterious despite the tongue's high tactile acuity, sensitivity, and relevance to ethologically important functions. We studied terminal morphologies and tactile responses of lingual afferents from the trigeminal ganglion. Fungiform papillae, the taste-bud-holding structures in the tongue, were convergently innervated by multiple Piezo2<sup>+</sup> trigeminal afferents, whereas single trigeminal afferents branched into multiple adjacent filiform papillae. In vivo single-unit recordings from the trigeminal ganglion revealed lingual low-threshold mechanoreceptors (LTMRs) with distinct tactile properties ranging from intermediately adapting (IA) to rapidly adapting (RA). The receptive fields of these LTMRs were mostly less than 0.1 mm<sup>2</sup> and concentrated at the tip of the tongue, resembling the distribution of fungiform papillae. Our results indicate that fungiform papillae are mechanosensory structures and suggest a simple model that links functional and anatomical properties of tactile sensory neurons in the tongue.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104772","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}
Pub Date : 2024-08-29DOI: 10.1016/j.celrep.2024.114675
Mireia Cordero, Liselotte Jauffred
In this issue of Cell Reports, Ma et al.1 identify causative regulatory links between self-organization in surface-attached bacterial colonies and the rate of horizontal gene transfers (conjugations) and subsequent selection of the newly arising population of recipient bacteria (transconjugants).
{"title":"Following plasmid propagation in complex bacterial communities.","authors":"Mireia Cordero, Liselotte Jauffred","doi":"10.1016/j.celrep.2024.114675","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114675","url":null,"abstract":"<p><p>In this issue of Cell Reports, Ma et al.<sup>1</sup> identify causative regulatory links between self-organization in surface-attached bacterial colonies and the rate of horizontal gene transfers (conjugations) and subsequent selection of the newly arising population of recipient bacteria (transconjugants).</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104759","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}
Pub Date : 2024-08-29DOI: 10.1016/j.celrep.2024.114685
Zoie Magri, David Jetton, Hayley I Muendlein, Wilson M Connolly, Hunter Russell, Irina Smirnova, Shruti Sharma, Stephen Bunnell, Alexander Poltorak
Signaling through classical death receptor Fas was mainly appreciated as a pro-death pathway until recent reports characterized pro-inflammatory outcomes of Fas-mediated activation in pathological contexts. How Fas signaling can switch to pro-inflammatory activation is poorly understood. Herein, we report that in macrophages and neutrophils, the Toll-like receptor (TLR) adapter CD14 determines the inflammatory output of Fas-mediated signaling. Our findings propose CD14 as a crucial chaperone of Fas receptor internalization in macrophages and neutrophils, resulting in Cd14-/- myeloid cells that are protected from FasL-induced apoptosis, activate nuclear factor κB (NF-κB), and release cytokines in response. As in TLR signaling, CD14 is also required for Fas to signal through the adaptor TRIF (TIR-domain-containing adapter-inducing interferon-β) and induce a pro-death complex. Our findings demonstrate that CD14 availability can determine the switch between Fas-mediated pro-death and pro-inflammatory outcomes by internalizing the receptor.
{"title":"CD14 is a decision-maker between Fas-mediated death and inflammation.","authors":"Zoie Magri, David Jetton, Hayley I Muendlein, Wilson M Connolly, Hunter Russell, Irina Smirnova, Shruti Sharma, Stephen Bunnell, Alexander Poltorak","doi":"10.1016/j.celrep.2024.114685","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114685","url":null,"abstract":"<p><p>Signaling through classical death receptor Fas was mainly appreciated as a pro-death pathway until recent reports characterized pro-inflammatory outcomes of Fas-mediated activation in pathological contexts. How Fas signaling can switch to pro-inflammatory activation is poorly understood. Herein, we report that in macrophages and neutrophils, the Toll-like receptor (TLR) adapter CD14 determines the inflammatory output of Fas-mediated signaling. Our findings propose CD14 as a crucial chaperone of Fas receptor internalization in macrophages and neutrophils, resulting in Cd14<sup>-/-</sup> myeloid cells that are protected from FasL-induced apoptosis, activate nuclear factor κB (NF-κB), and release cytokines in response. As in TLR signaling, CD14 is also required for Fas to signal through the adaptor TRIF (TIR-domain-containing adapter-inducing interferon-β) and induce a pro-death complex. Our findings demonstrate that CD14 availability can determine the switch between Fas-mediated pro-death and pro-inflammatory outcomes by internalizing the receptor.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104755","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}