Celia Lerma-Martin, Pau Badia-i-Mompel, Ricardo O. Ramirez Flores, Patricia Sekol, Philipp S. L. Schäfer, Christian J. Riedl, Annika Hofmann, Thomas Thäwel, Florian Wünnemann, Miguel A. Ibarra-Arellano, Tim Trobisch, Philipp Eisele, Denis Schapiro, Maximilian Haeussler, Simon Hametner, Julio Saez-Rodriguez, Lucas Schirmer
{"title":"Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions","authors":"Celia Lerma-Martin, Pau Badia-i-Mompel, Ricardo O. Ramirez Flores, Patricia Sekol, Philipp S. L. Schäfer, Christian J. Riedl, Annika Hofmann, Thomas Thäwel, Florian Wünnemann, Miguel A. Ibarra-Arellano, Tim Trobisch, Philipp Eisele, Denis Schapiro, Maximilian Haeussler, Simon Hametner, Julio Saez-Rodriguez, Lucas Schirmer","doi":"10.1038/s41593-024-01796-z","DOIUrl":"10.1038/s41593-024-01796-z","url":null,"abstract":"Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood. We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas. We identified niches such as perivascular spaces, the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype. Focusing on the inflamed rim of chronic active lesions, we uncovered cell–cell communication events between myeloid, endothelial and glial cell types. Our results provide insight into the cellular composition, multicellular programs and intercellular communication in tissue niches along the conversion from a homeostatic to a dysfunctional state underlying lesion progression in MS. Lerma-Martin et al. generated a paired single-nucleus RNA sequencing and spatial transcriptomics dataset from subcortical multiple sclerosis lesions, identifying spatial niches and key cell interactions driving inflammation and disease progression at the lesion rim.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2354-2365"},"PeriodicalIF":21.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01796-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580336","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}
Huasheng Yu, Saad S. Nagi, Dmitry Usoskin, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Hanying Yan, Suna Li Cranfill, Mayank Gautam, Yijing Su, You Lu, James Wymer, Max Glanz, Phillip Albrecht, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Andrew Marshall, Frank L. Rice, Mingyao Li, Håkan Olausson, Patrik Ernfors, Wenqin Luo
{"title":"Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation","authors":"Huasheng Yu, Saad S. Nagi, Dmitry Usoskin, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Hanying Yan, Suna Li Cranfill, Mayank Gautam, Yijing Su, You Lu, James Wymer, Max Glanz, Phillip Albrecht, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Andrew Marshall, Frank L. Rice, Mingyao Li, Håkan Olausson, Patrik Ernfors, Wenqin Luo","doi":"10.1038/s41593-024-01794-1","DOIUrl":"10.1038/s41593-024-01794-1","url":null,"abstract":"The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons—critical information to decipher their functions—are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types. These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization. Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types. Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types. In summary, by employing single-soma deep RNA-seq and spatial transcriptomics, we generated an hDRG neuron atlas, which provides insights into human somatosensory physiology and serves as a foundation for translational work. Dorsal root ganglia (DRGs) contain a plethora of neuron types. The authors show that the existence of human-specific DRG neuronal types and microneurography recordings reveal distinct temperature-sensing properties across human sensory afferent types.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2326-2340"},"PeriodicalIF":21.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01794-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574473","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}
Kevin G. C. Mizes, Jack Lindsey, G. Sean Escola, Bence P. Ölveczky
{"title":"The role of motor cortex in motor sequence execution depends on demands for flexibility","authors":"Kevin G. C. Mizes, Jack Lindsey, G. Sean Escola, Bence P. Ölveczky","doi":"10.1038/s41593-024-01792-3","DOIUrl":"10.1038/s41593-024-01792-3","url":null,"abstract":"The role of the motor cortex in executing motor sequences is widely debated, with studies supporting disparate views. Here we probe the degree to which the motor cortex’s engagement depends on task demands, specifically whether its role differs for highly practiced, or ‘automatic’, sequences versus flexible sequences informed by external cues. To test this, we trained rats to generate three-element motor sequences either by overtraining them on a single sequence or by having them follow instructive visual cues. Lesioning motor cortex showed that it is necessary for flexible cue-driven motor sequences but dispensable for single automatic behaviors trained in isolation. However, when an automatic motor sequence was practiced alongside the flexible task, it became motor cortex dependent, suggesting that an automatic motor sequence fails to consolidate subcortically when the same sequence is produced also in a flexible context. A simple neural network model recapitulated these results and offered a circuit-level explanation. Our results critically delineate the role of the motor cortex in motor sequence execution, describing the conditions under which it is engaged and the functions it fulfills, thus reconciling seemingly conflicting views about motor cortex’s role in motor sequence generation. Motor cortex is required for flexible motor sequences informed by sensory cues but not for single automatic sequences. However, training automatic sequences alongside flexible ones interferes with their subcortical consolidation.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2466-2475"},"PeriodicalIF":21.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574472","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":"Astrocytes facilitate brain metastases","authors":"George Andrew S. Inglis","doi":"10.1038/s41593-024-01805-1","DOIUrl":"10.1038/s41593-024-01805-1","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2053-2053"},"PeriodicalIF":21.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574471","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":"Dissecting human brain connectivity across biophysical scales","authors":"","doi":"10.1038/s41593-024-01789-y","DOIUrl":"10.1038/s41593-024-01789-y","url":null,"abstract":"Neuroscience has identified components that give rise to cognitive function, including molecules, synapses, and brain anatomy, but how connectivity arises from these parts is challenging to uncover. We acquired measurements across these biophysical scales in 98 people and showed that their multiscale cooperation explains person-to-person variability in brain connectivity.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2054-2055"},"PeriodicalIF":21.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561848","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}
Bernard Ng, Shinya Tasaki, Kelsey M. Greathouse, Courtney K. Walker, Ada Zhang, Sydney Covitz, Matt Cieslak, Audrey J. Weber, Ashley B. Adamson, Julia P. Andrade, Emily H. Poovey, Kendall A. Curtis, Hamad M. Muhammad, Jakob Seidlitz, Ted Satterthwaite, David A. Bennett, Nicholas T. Seyfried, Jacob Vogel, Chris Gaiteri, Jeremy H. Herskowitz
{"title":"Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity","authors":"Bernard Ng, Shinya Tasaki, Kelsey M. Greathouse, Courtney K. Walker, Ada Zhang, Sydney Covitz, Matt Cieslak, Audrey J. Weber, Ashley B. Adamson, Julia P. Andrade, Emily H. Poovey, Kendall A. Curtis, Hamad M. Muhammad, Jakob Seidlitz, Ted Satterthwaite, David A. Bennett, Nicholas T. Seyfried, Jacob Vogel, Chris Gaiteri, Jeremy H. Herskowitz","doi":"10.1038/s41593-024-01788-z","DOIUrl":"10.1038/s41593-024-01788-z","url":null,"abstract":"Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for synaptic structures and functions, energy metabolism and RNA processing. By integrating data at the genetic, molecular, subcellular and tissue levels, we link specific biochemical changes at synapses to connectivity between brain regions. These results demonstrate the feasibility of integrating data from vastly different biophysical scales to provide a more comprehensive understanding of brain connectivity. Integration of postmortem molecular and dendritic spine morphological measurements enables the detection of microscale molecules associated with person-to-person variability in macroscale brain connectivity estimated from antemortem neuroimaging.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 11","pages":"2240-2252"},"PeriodicalIF":21.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01788-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555823","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":"Ernest Arenas (1962–2024)","authors":"Patrik Ernfors, Gonçalo Castelo-Branco, Per Uhlén, Sten Linnarsson, Ulrika Marklund, Jens Hjerling-Leffler, Onur Dagliyan","doi":"10.1038/s41593-024-01797-y","DOIUrl":"10.1038/s41593-024-01797-y","url":null,"abstract":"Ernest Arenas, Professor at the Karolinska Institutet, passed away on 15 September 2024 at the age of 62 in Stockholm, Sweden. Ernest made unique contributions to the field of Parkinson’s disease research, with a strong commitment to developing improved treatment strategies through cell replacement therapy.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2267-2268"},"PeriodicalIF":21.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01797-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519252","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}