Marco Colonna, Genevieve Konopka, Shane A. Liddelow, Tomasz Nowakowski, Rajeshwar Awatramani, Helen S. Bateup, Cathryn R. Cadwell, Emre Caglayan, Jerry L. Chen, Jesse Gillis, Martin Kampmann, Fenna Krienen, Samuel E. Marsh, Michelle Monje, Michael R. O’Dea, Rickie Patani, Alex A. Pollen, Francisco J. Quintana, Marissa Scavuzzo, Matthew Schmitz, Steven A. Sloan, Paul J. Tesar, Jessica Tollkuhn, Maria Antonietta Tosches, Madeleine E. Urbanek, Jonathan M. Werner, Omer A. Bayraktar, Ozgun Gokce, Naomi Habib
{"title":"Implementation and validation of single-cell genomics experiments in neuroscience","authors":"Marco Colonna, Genevieve Konopka, Shane A. Liddelow, Tomasz Nowakowski, Rajeshwar Awatramani, Helen S. Bateup, Cathryn R. Cadwell, Emre Caglayan, Jerry L. Chen, Jesse Gillis, Martin Kampmann, Fenna Krienen, Samuel E. Marsh, Michelle Monje, Michael R. O’Dea, Rickie Patani, Alex A. Pollen, Francisco J. Quintana, Marissa Scavuzzo, Matthew Schmitz, Steven A. Sloan, Paul J. Tesar, Jessica Tollkuhn, Maria Antonietta Tosches, Madeleine E. Urbanek, Jonathan M. Werner, Omer A. Bayraktar, Ozgun Gokce, Naomi Habib","doi":"10.1038/s41593-024-01814-0","DOIUrl":"10.1038/s41593-024-01814-0","url":null,"abstract":"Single-cell or single-nucleus transcriptomics is a powerful tool for identifying cell types and cell states. However, hypotheses derived from these assays, including gene expression information, require validation, and their functional relevance needs to be established. The choice of validation depends on numerous factors. Here, we present types of orthogonal and functional validation experiment to strengthen preliminary findings obtained using single-cell and single-nucleus transcriptomics as well as the challenges and limitations of these approaches. Single-cell or single-nucleus RNA-sequencing experiments form a basis for biological insights about cell types and states, but they require orthogonal experiments to confirm the functional relevance of their findings. Here the authors discuss options to support such findings and their challenges.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2310-2325"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Igor Adameyko, Trygve Bakken, Aparna Bhaduri, Chintan Chhatbar, Mariella G. Filbin, David Gate, Hannah Hochgerner, Chang Nam Kim, Jordan Krull, Gioele La Manno, Qingyun Li, Sten Linnarsson, Qin Ma, Christian Mayer, Vilas Menon, Patricia Nano, Marco Prinz, Steve Quake, Christopher A. Walsh, Jin Yang, Omer Ali Bayraktar, Ozgun Gokce, Naomi Habib, Genevieve Konopka, Shane A. Liddelow, Tomasz J. Nowakowski
{"title":"Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system","authors":"Igor Adameyko, Trygve Bakken, Aparna Bhaduri, Chintan Chhatbar, Mariella G. Filbin, David Gate, Hannah Hochgerner, Chang Nam Kim, Jordan Krull, Gioele La Manno, Qingyun Li, Sten Linnarsson, Qin Ma, Christian Mayer, Vilas Menon, Patricia Nano, Marco Prinz, Steve Quake, Christopher A. Walsh, Jin Yang, Omer Ali Bayraktar, Ozgun Gokce, Naomi Habib, Genevieve Konopka, Shane A. Liddelow, Tomasz J. Nowakowski","doi":"10.1038/s41593-024-01827-9","DOIUrl":"10.1038/s41593-024-01827-9","url":null,"abstract":"Single-cell and single-nucleus genomic approaches can provide unbiased and multimodal insights. Here, we discuss what constitutes a molecular cell atlas and how to leverage single-cell omics data to generate hypotheses and gain insights into cell transitions in development and disease of the nervous system. We share points of reflection on what to consider during study design and implementation as well as limitations and pitfalls. This Review provides insights for construction of molecular cell atlases and outlines key study design considerations. The authors emphasize the power of single-cell and single-nucleus genomics in revealing cellular transitions during nervous system development and disease.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2278-2291"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boyan Bonev, Castelo-Branco Gonçalo, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Bayraktar, Naomi Habib, Tomasz J. Nowakowski
{"title":"Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery","authors":"Boyan Bonev, Castelo-Branco Gonçalo, Fei Chen, Simone Codeluppi, M. Ryan Corces, Jean Fan, Myriam Heiman, Kenneth Harris, Fumitaka Inoue, Manolis Kellis, Ariel Levine, Mo Lotfollahi, Chongyuan Luo, Kristen R. Maynard, Mor Nitzan, Vijay Ramani, Rahul Satijia, Lucas Schirmer, Yin Shen, Na Sun, Gilad S. Green, Fabian Theis, Xiao Wang, Joshua D. Welch, Ozgun Gokce, Genevieve Konopka, Shane Liddelow, Evan Macosko, Omer Bayraktar, Naomi Habib, Tomasz J. Nowakowski","doi":"10.1038/s41593-024-01806-0","DOIUrl":"10.1038/s41593-024-01806-0","url":null,"abstract":"Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells. Here, we summarize the most promising and robust technologies in these areas, discuss their strengths and limitations and discuss key computational approaches for analysis of these complex datasets. We highlight how data sharing and integration, documentation, visualization and benchmarking of results contribute to transparency, reproducibility, collaboration and democratization in neuroscience, and discuss needs and opportunities for future technology development and analysis. This review provides an overview of analysis and experimental design of single-cell omics in the brain, emphasizing epigenomics and spatial omics. The authors discuss how the computational and experimental designs are interlinked, with both being guided by the biological questions.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2292-2309"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federica Maltese, Giada Pacinelli, Anna Monai, Fabrizio Bernardi, Ana Marta Capaz, Marco Niello, Roman Walle, Noelia de Leon, Francesca Managò, Felix Leroy, Francesco Papaleo
{"title":"Self-experience of a negative event alters responses to others in similar states through prefrontal cortex CRF mechanisms","authors":"Federica Maltese, Giada Pacinelli, Anna Monai, Fabrizio Bernardi, Ana Marta Capaz, Marco Niello, Roman Walle, Noelia de Leon, Francesca Managò, Felix Leroy, Francesco Papaleo","doi":"10.1038/s41593-024-01816-y","DOIUrl":"10.1038/s41593-024-01816-y","url":null,"abstract":"Our own experience of emotional events influences how we approach and react to others’ emotions. Here we observe that mice exhibit divergent interindividual responses to others in stress (that is, preference or avoidance) only if they have previously experienced the same aversive event. These responses are estrus dependent in females and dominance dependent in males. Notably, silencing the expression of the corticotropin-releasing factor (CRF) within the medial prefrontal cortex (mPFC) attenuates the impact of stress self-experience on the reaction to others’ stress. In vivo microendoscopic calcium imaging revealed that mPFC CRF neurons are activated more toward others’ stress only following the same negative self-experience. Optogenetic manipulations confirmed that higher activation of mPFC CRF neurons is responsible for the switch from preference to avoidance of others in stress, but only following stress self-experience. These results provide a neurobiological substrate underlying how an individual’s emotional experience influences their approach toward others in a negative emotional state. Maltese et al. show in mice that experiencing an adverse event affects future interaction with others experiencing the same stressor. These self-experience socioemotional reactions are orchestrated by the corticotropin-releasing factor system in the medial prefrontal cortex.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 1","pages":"122-136"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous representations of the past and future","authors":"Henrietta Howells","doi":"10.1038/s41593-024-01840-y","DOIUrl":"10.1038/s41593-024-01840-y","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2269-2269"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Parallel gut-to-brain pathways orchestrate feeding behaviors","authors":"Hongyun Wang, Runxiang Lou, Yunfeng Wang, Liufang Hao, Qiushi Wang, Rui Li, Jiayi Su, Shuhan Liu, Xiangyu Zhou, Xinwei Gao, Qianxi Hao, Zihe Chen, Yibo Xu, Chongwei Wu, Yang Zheng, Qingchun Guo, Ling Bai","doi":"10.1038/s41593-024-01828-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01828-8","url":null,"abstract":"<p>The caudal nucleus of the solitary tract (cNTS) in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways. However, the mechanisms by which cNTS neurons transform these signals into behaviors remain debated. We analyzed 18 cNTS-Cre mouse lines and cataloged the dynamics of nine cNTS cell types during feeding. We show that <i>Th</i><sup>+</sup> cNTS neurons encode esophageal mechanical distension and transient gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed. By contrast, <i>Gcg</i><sup>+</sup> cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference. These nutritive signals are conveyed through a portal vein–spinal ascending pathway rather than vagal sensory neurons. Our findings underscore distinctions among cNTS subtypes marked by differences in temporal dynamics, sensory modalities, associated visceral organs and ascending sensory pathways, all of which contribute to specific functions in coordinated feeding regulation.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"13 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Focus on single-cell genomics","authors":"","doi":"10.1038/s41593-024-01844-8","DOIUrl":"10.1038/s41593-024-01844-8","url":null,"abstract":"Single-cell genomics is deepening our understanding of the nervous system and shedding light on the heterogeneity of its cells. This focus issue of Nature Neuroscience celebrates recent methodological and analytical advances in single-cell genomics, highlights principles of study design, and aims to encourage collaboration between cellular, molecular and systems neuroscientists.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2263-2263"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01844-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enteric neurons and gut immunity","authors":"George Andrew S. Inglis","doi":"10.1038/s41593-024-01841-x","DOIUrl":"10.1038/s41593-024-01841-x","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2269-2269"},"PeriodicalIF":21.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}