{"title":"Paired C-type lectin receptors mediate specific recognition of divergent oomycete pathogens in C. elegans.","authors":"Kenneth Liu, Manish Grover, Franziska Trusch, Christina Vagena-Pantoula, Domenica Ippolito, Michalis Barkoulas","doi":"10.1016/j.celrep.2024.114906","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114906","url":null,"abstract":"<p><p>Innate immune responses can be triggered upon detection of pathogen- or damage-associated molecular patterns by host receptors that are often present on the surface of immune cells. While invertebrates like Caenorhabditis elegans lack professional immune cells, they still mount pathogen-specific responses. However, the identity of host receptors in the nematode remains poorly understood. Here, we show that C-type lectin receptors mediate species-specific recognition of divergent oomycetes in C. elegans. A CLEC-27/CLEC-35 pair is essential for recognition of the oomycete Myzocytiopsis humicola, while a CLEC-26/CLEC-36 pair is required for detection of Haptoglossa zoospora. Both clec pairs are transcriptionally regulated through a shared promoter by the conserved PRD-like homeodomain transcription factor CEH-37/OTX2 and act in sensory neurons and the anterior intestine to trigger a protective immune response in the epidermis. This system enables redundant tissue sensing of oomycete threats through canonical CLEC receptors and host defense via cross-tissue communication.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114906"},"PeriodicalIF":7.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496008","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}
Cell reportsPub Date : 2024-10-25DOI: 10.1016/j.celrep.2024.114779
Izabella Skulimowska, Jan Morys, Justyna Sosniak, Monika Gonka, Gunsagar Gulati, Rahul Sinha, Kacper Kowalski, Sylwester Mosiolek, Irving L Weissman, Alicja Jozkowicz, Agata Szade, Krzysztof Szade
{"title":"Polyclonal regeneration of mouse bone marrow endothelial cells after irradiative conditioning.","authors":"Izabella Skulimowska, Jan Morys, Justyna Sosniak, Monika Gonka, Gunsagar Gulati, Rahul Sinha, Kacper Kowalski, Sylwester Mosiolek, Irving L Weissman, Alicja Jozkowicz, Agata Szade, Krzysztof Szade","doi":"10.1016/j.celrep.2024.114779","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114779","url":null,"abstract":"<p><p>Bone marrow endothelial cells (BM-ECs) are the essential components of the BM niche and support the function of hematopoietic stem cells (HSCs). However, conditioning for HSC transplantation causes damage to the recipients' BM-ECs and may lead to transplantation-related morbidity. Here, we investigated the cellular and clonal mechanisms of BM-EC regeneration after irradiative conditioning. Using single-cell RNA sequencing, imaging, and flow cytometry, we revealed how the heterogeneous pool of BM-ECs changes during regeneration from irradiation stress. Next, we developed a single-cell in vitro clonogenic assay and demonstrated that all EC fractions hold a high potential to reenter the cell cycle and form vessel-like structures. Finally, we used Rainbow mice and a machine-learning-based model to show that the regeneration of BM-ECs after irradiation is mostly polyclonal and driven by the broad fraction of BM-ECs; however, the cell output among clones varies at later stages of regeneration.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114779"},"PeriodicalIF":7.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567449","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}
Cell reportsPub Date : 2024-10-25DOI: 10.1016/j.celrep.2024.114902
Lin Zhang, Yan Shi, Wenfang Gong, Guang Zhao, Shixin Xiao, Hai Lin, Yanmin Li, Zhenyang Liao, Shengcheng Zhang, Guanxing Hu, Ziqi Ye, Haifeng Wang, Zhiqiang Xia, Yekun Yang, Heping Cao, Shengjun Zhong, Xingtan Zhang, Deyi Yuan
{"title":"The tetraploid Camellia oleifera genome provides insights into evolution, agronomic traits, and genetic architecture of oil Camellia plants.","authors":"Lin Zhang, Yan Shi, Wenfang Gong, Guang Zhao, Shixin Xiao, Hai Lin, Yanmin Li, Zhenyang Liao, Shengcheng Zhang, Guanxing Hu, Ziqi Ye, Haifeng Wang, Zhiqiang Xia, Yekun Yang, Heping Cao, Shengjun Zhong, Xingtan Zhang, Deyi Yuan","doi":"10.1016/j.celrep.2024.114902","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114902","url":null,"abstract":"<p><p>Camellia oleifera is an economically important woody oil plant. Complex ploidy and lack of genomic information have seriously hindered the molecular breeding of C. oleifera. Here, we present an 11.43-Gb haplotype-resolved, chromosome-level genome assembly of tetraploid C. oleifera (COL-tetra). Methods employed in this study support the conclusion that COL-tetra is an autotetraploid and probably originates from genome doubling of the diploid C. brevistyla. In addition, DNA methylation plays a significant role in imbalanced allelic expression and seed development. Genetic divergence analyses reveal significant differentiation signals for flowering time between spring-flowering and autumn-flowering oil Camellia species, which probably account for reproductive isolation between species with distinct flowering times. Strong introgression signals are detected between COL-tetra and C. sasanqua and between C. vietnamensis and COL-hexa, which might affect the development of agronomic traits and environmental adaptability. This study provides valuable insights into the evolution, agronomic trait development, and genetic architecture of oil Camellia plants.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114902"},"PeriodicalIF":7.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567451","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}
Cell reportsPub Date : 2024-10-24DOI: 10.1016/j.celrep.2024.114887
Carlos A Pinzon-Arteaga, Ryan O'Hara, Alice Mazzagatti, Emily Ballard, Yingying Hu, Alex Pan, Daniel A Schmitz, Yulei Wei, Masahiro Sakurai, Peter Ly, Laura A Banaszynski, Jun Wu
{"title":"TASOR expression in naive embryonic stem cells safeguards their developmental potential.","authors":"Carlos A Pinzon-Arteaga, Ryan O'Hara, Alice Mazzagatti, Emily Ballard, Yingying Hu, Alex Pan, Daniel A Schmitz, Yulei Wei, Masahiro Sakurai, Peter Ly, Laura A Banaszynski, Jun Wu","doi":"10.1016/j.celrep.2024.114887","DOIUrl":"10.1016/j.celrep.2024.114887","url":null,"abstract":"<p><p>The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs. Notably, the survival of Tasor knockout PSCs during this transition can be restored by inhibiting caspase or deleting the mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to cell death specifically in cells exiting naive pluripotency. Our findings highlight the importance of epigenetic programs established in naive pluripotency for normal development.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114887"},"PeriodicalIF":7.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496014","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":"STUB1-mediated ubiquitination and degradation of NSUN2 promotes hepatocyte ferroptosis by decreasing m<sup>5</sup>C methylation of Gpx4 mRNA.","authors":"Xiaotian Zhang, Yihua Zhang, Rongrong Li, Yibo Li, Qi Wang, Ying Wang, Xinying Chen, Weihua Wang, Erli Pang, Yanyan Li, Jia Wang, Jinping Zheng, Junjie Zhang","doi":"10.1016/j.celrep.2024.114885","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114885","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent cell death that occurs due to the peroxidation of phospholipids in the cell membrane. In this study, we find that the protein level of NSUN2 is significantly decreased in hepatocyte ferroptosis. This is attributed to STUB1-mediated ubiquitination of NSUN2 at lysines 457 and 654, promoting NSUN2 degradation in ferroptosis. Selenoprotein glutathione peroxidase 4 (GPX4) is a prominent suppressor of ferroptosis. We find that downregulation of NSUN2 diminishes m<sup>5</sup>C methylation of Gpx4 mRNA 3' UTR. The reduction of NSUN2-mediated Gpx4 mRNA m<sup>5</sup>C methylation abrogates the interaction between SBP2 and the selenocysteine insertion sequence (SECIS) and leads to inhibition of GPX4 protein expression. Lower GPX4 expression promotes hepatocyte ferroptosis in vivo and in vitro, which is reversed by restoration of NSUN2. These findings shed light on the mechanism of NSUN2 degradation and also indicate that the STUB1-NSUN2-GPX4 axis plays a regulatory role in hepatocyte ferroptosis.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114885"},"PeriodicalIF":7.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496013","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}
Cell reportsPub Date : 2024-10-23DOI: 10.1016/j.celrep.2024.114875
Sunita Keshari, Alexander S Shavkunov, Qi Miao, Akata Saha, Tomoyuki Minowa, Martina Molgora, Charmelle D Williams, Mehdi Chaib, Anna M Highsmith, Josué E Pineda, Sayan Alekseev, Elise Alspach, Kenneth H Hu, Marco Colonna, Kristen E Pauken, Ken Chen, Matthew M Gubin
{"title":"Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy.","authors":"Sunita Keshari, Alexander S Shavkunov, Qi Miao, Akata Saha, Tomoyuki Minowa, Martina Molgora, Charmelle D Williams, Mehdi Chaib, Anna M Highsmith, Josué E Pineda, Sayan Alekseev, Elise Alspach, Kenneth H Hu, Marco Colonna, Kristen E Pauken, Ken Chen, Matthew M Gubin","doi":"10.1016/j.celrep.2024.114875","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114875","url":null,"abstract":"<p><p>The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1<sup>+</sup>TCF-1<sup>+</sup> neoAg-specific CD8 T cells in tumors. Anti-CTLA-4 and/or anti-PD-1 ICT promotes intratumoral TCF-1<sup>-</sup> neoAg-specific CD8 T cells, although their phenotype depends in part on the specific ICT used. Anti-CTLA-4 also prompts substantial changes to CD4 T cells, including induction of ICOS<sup>+</sup>Bhlhe40<sup>+</sup> T helper 1 (Th1)-like cells. Although neoAg vaccines or ICTs expand iNOS<sup>+</sup> macrophages, neoAg vaccines maintain CX3CR1<sup>+</sup>CD206<sup>+</sup> macrophages expressing the TREM2 receptor, unlike ICT, which suppresses them. TREM2 blockade enhances neoAg vaccine efficacy and is associated with fewer CX3CR1<sup>+</sup>CD206<sup>+</sup> macrophages and induction of neoAg-specific CD8 T cells. Our findings highlight different mechanisms underlying neoAg vaccines and different forms of ICT and identify combinatorial therapies to enhance neoAg vaccine efficacy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114875"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496002","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}
Cell reportsPub Date : 2024-10-23DOI: 10.1016/j.celrep.2024.114898
Yu-Qiu Jiang, Daniel K Lee, Wanyi Guo, Minghua Li, Qian Sun
{"title":"Hypothalamic regulation of hippocampal CA1 interneurons by the supramammillary nucleus.","authors":"Yu-Qiu Jiang, Daniel K Lee, Wanyi Guo, Minghua Li, Qian Sun","doi":"10.1016/j.celrep.2024.114898","DOIUrl":"10.1016/j.celrep.2024.114898","url":null,"abstract":"<p><p>The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP<sup>+</sup>) and neuron-derived neurotrophic factor-expressing (NDNF<sup>+</sup>) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV<sup>+</sup>) or somatostatin-expressing (SOM<sup>+</sup>) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114898"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496006","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}
Cell reportsPub Date : 2024-10-23DOI: 10.1016/j.celrep.2024.114894
Athena Boutou, Ilias Roufagalas, Katerina Politopoulou, Spyros Tastsoglou, Maya Abouzeid, Giorgos Skoufos, Laia Verdu de Juan, Jeong Hun Ko, Vasiliki Kyrargyri, Artemis G Hatzigeorgiou, Christopher J Barnum, Raymond J Tesi, Jan Bauer, Hans Lassmann, Michael R Johnson, Lesley Probert
{"title":"Microglia regulate cortical remyelination via TNFR1-dependent phenotypic polarization.","authors":"Athena Boutou, Ilias Roufagalas, Katerina Politopoulou, Spyros Tastsoglou, Maya Abouzeid, Giorgos Skoufos, Laia Verdu de Juan, Jeong Hun Ko, Vasiliki Kyrargyri, Artemis G Hatzigeorgiou, Christopher J Barnum, Raymond J Tesi, Jan Bauer, Hans Lassmann, Michael R Johnson, Lesley Probert","doi":"10.1016/j.celrep.2024.114894","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114894","url":null,"abstract":"<p><p>Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here, we show that microglia-specific deletion of tumor necrosis factor receptor 1 (TNFR1) and pharmacological inhibition of soluble TNF (solTNF) or downstream interleukin-1 receptor (IL-1R) allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery. Single-cell transcriptomic analysis of cortex at disease onset reveals that solTNF inhibition enhances reparative IL-10-responsive while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveals earlier recovery upon therapeutic loss of microglia TNFR1. The functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/caspase-11 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114894"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496007","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}
Cell reportsPub Date : 2024-10-23DOI: 10.1016/j.celrep.2024.114869
Rebecca E Wagner, Leonie Arnetzl, Thiago Britto-Borges, Anke Heit-Mondrzyk, Ali Bakr, Etienne Sollier, Nikoletta A Gkatza, Jasper Panten, Sylvain Delaunay, Daniela Sohn, Peter Schmezer, Duncan T Odom, Karin Müller-Decker, Christoph Plass, Christoph Dieterich, Pavlo Lutsik, Susanne Bornelöv, Michaela Frye
{"title":"SRSF2 safeguards efficient transcription of DNA damage and repair genes.","authors":"Rebecca E Wagner, Leonie Arnetzl, Thiago Britto-Borges, Anke Heit-Mondrzyk, Ali Bakr, Etienne Sollier, Nikoletta A Gkatza, Jasper Panten, Sylvain Delaunay, Daniela Sohn, Peter Schmezer, Duncan T Odom, Karin Müller-Decker, Christoph Plass, Christoph Dieterich, Pavlo Lutsik, Susanne Bornelöv, Michaela Frye","doi":"10.1016/j.celrep.2024.114869","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114869","url":null,"abstract":"<p><p>The serine-/arginine-rich splicing factor 2 (SRSF2) plays pivotal roles in pre-mRNA processing and gene transcription. Recurrent mutations, particularly a proline-to-histidine substitution at position 95 (P95H), are common in neoplastic diseases. Here, we assess SRSF2's diverse functions in squamous cell carcinoma. We show that SRSF2 deletion or homozygous P95H mutation both cause extensive DNA damage leading to cell-cycle arrest. Mechanistically, SRSF2 regulates efficient bi-directional transcription of DNA replication and repair genes, independent from its function in splicing. Further, SRSF2 haploinsufficiency induces DNA damage without halting the cell cycle. Exposing mouse skin to tumor-promoting carcinogens enhances the clonal expansion of heterozygous Srsf2 P95H epidermal cells but unexpectedly inhibits tumor formation. To survive carcinogen treatment, Srsf2 P95H<sup>+/-</sup> cells undergo substantial transcriptional rewiring and restore bi-directional gene expression. Thus, our study underscores SRSF2's importance in regulating transcription to orchestrate the cell cycle and the DNA damage response.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114869"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496012","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}
Cell reportsPub Date : 2024-10-23DOI: 10.1016/j.celrep.2024.114876
Cynthia M Arokiaraj, Michael J Leone, Michael Kleyman, Alexander Chamessian, Myung-Chul Noh, BaDoi N Phan, Bettega C Lopes, Kelly A Corrigan, Vijay Kiran Cherupally, Deepika Yeramosu, Michael E Franusich, Riya Podder, Sumitra Lele, Stephanie Shiers, Byungsoo Kang, Meaghan M Kennedy, Viola Chen, Ziheng Chen, Hansruedi Mathys, Richard P Dum, David A Lewis, Yawar Qadri, Theodore J Price, Andreas R Pfenning, Rebecca P Seal
{"title":"Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.","authors":"Cynthia M Arokiaraj, Michael J Leone, Michael Kleyman, Alexander Chamessian, Myung-Chul Noh, BaDoi N Phan, Bettega C Lopes, Kelly A Corrigan, Vijay Kiran Cherupally, Deepika Yeramosu, Michael E Franusich, Riya Podder, Sumitra Lele, Stephanie Shiers, Byungsoo Kang, Meaghan M Kennedy, Viola Chen, Ziheng Chen, Hansruedi Mathys, Richard P Dum, David A Lewis, Yawar Qadri, Theodore J Price, Andreas R Pfenning, Rebecca P Seal","doi":"10.1016/j.celrep.2024.114876","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114876","url":null,"abstract":"<p><p>Key mechanisms underlying chronic pain occur within the dorsal horn. Genome-wide association studies (GWASs) have identified genetic variants predisposed to chronic pain. However, most of these variants lie within regulatory non-coding regions that have not been linked to spinal cord biology. Here, we take a multi-species approach to determine whether chronic pain variants impact the regulatory genomics of dorsal horn neurons. First, we generate a large rhesus macaque single-nucleus RNA sequencing (snRNA-seq) atlas and integrate it with available human and mouse datasets to produce a single unified, species-conserved atlas of neuron subtypes. Cellular-resolution spatial transcriptomics in mouse shows the precise laminar location of these neuron subtypes, consistent with our analysis of neuron-subtype-selective markers in macaque. Using this cross-species framework, we generate a mouse single-nucleus open chromatin atlas of regulatory elements that shows strong and selective relationships between the neuron-subtype-specific chromatin regions and variants from major chronic pain GWASs.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114876"},"PeriodicalIF":7.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496011","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}
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