Cell ResearchPub Date : 2026-03-25DOI: 10.1038/s41422-026-01240-w
Soochi Kim, Seung Pil Pack, Thomas A. Rando
{"title":"Transcriptomic advances in studies of muscle stem cell aging: From bulk to single-cell and beyond","authors":"Soochi Kim, Seung Pil Pack, Thomas A. Rando","doi":"10.1038/s41422-026-01240-w","DOIUrl":"10.1038/s41422-026-01240-w","url":null,"abstract":"Advances in transcriptomic technologies have progressively transformed the questions we can ask and answer about muscle stem cells (MuSCs) during aging. Early microarray and bulk RNA sequencing studies established foundational population-level signatures of aged MuSCs, including attenuation of myogenic and metabolic programs as well as induction of inflammatory and stress-associated transcription. However, these averaged readouts obscured cell-to-cell variability and rare functional states. The transition to single-cell and single-nucleus RNA sequencing marked a turning point by resolving MuSC heterogeneity and revealing that MuSC aging is not purely stochastic. Instead, aged MuSC pools show reproducible changes in state composition, delayed or altered myogenic lineage progression, and selective vulnerability of specific functional subsets. Emerging spatial transcriptomic approaches, although still limited by sensitivity and cell-type discrimination in muscle, are beginning to place these MuSC states into their native tissue context, directly linking transcriptional states, niche organization, and age-associated remodeling. In parallel, integrative multi-omic designs that pair transcriptomics with chromatin accessibility and metabolic measurements have strengthened mechanistic connections among age-associated gene programs, epigenetic remodeling, and metabolic state shifts. Finally, computational frameworks — including trajectory inference, dynamic modeling, and machine learning — are increasingly applied to high-dimensional transcriptomic data to predict aging trajectories and identify candidate rejuvenation targets. In this Perspective, we trace the evolution of transcriptomic technologies through the lens of MuSC aging and highlight how increasing resolution has reframed core models of MuSC decline and plasticity.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 5","pages":"313-321"},"PeriodicalIF":25.9,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-03-23DOI: 10.1038/s41422-026-01235-7
Hui Xiong,Daniel Amado-Ruiz,Tessa R Lodder,Mireille Toebes,Ton N Schumacher,Hailan Hu,Helmut W Kessels
{"title":"Social status impacts T-cell responses through synapse strength in the prefrontal cortex.","authors":"Hui Xiong,Daniel Amado-Ruiz,Tessa R Lodder,Mireille Toebes,Ton N Schumacher,Hailan Hu,Helmut W Kessels","doi":"10.1038/s41422-026-01235-7","DOIUrl":"https://doi.org/10.1038/s41422-026-01235-7","url":null,"abstract":"Social status affects health by influencing the capacity of the immune system to respond to infection and disease. However, the neuronal mechanisms that explain how social status causes individual differences in immunity are unknown. In this study, we observed that among social groups of four male mice, those ranked second in the hierarchy displayed, on average, superior T-cell responses upon vaccination. The greater T-cell responses in second-ranked mice were dependent on synaptic communication ability in the brain. The brain circuits that control position in the social hierarchy are beginning to emerge, with the dorsomedial prefrontal cortex (dmPFC) as a central player. We found that selectively increasing the strength of dmPFC synapses or increasing the activity of dmPFC neurons was sufficient to boost antigen-specific T-cell percentages in response to vaccination. These findings reveal a causal link between the dmPFC and the peripheral immune system, enriching our understanding of the origin of health problems caused by social inequality.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"146 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495048","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 ResearchPub Date : 2026-03-19DOI: 10.1038/s41422-026-01237-5
Victoria L. Palfini, Matthew N. Rasband
{"title":"AXIS of excitability: microglia promote neuronal firing","authors":"Victoria L. Palfini, Matthew N. Rasband","doi":"10.1038/s41422-026-01237-5","DOIUrl":"10.1038/s41422-026-01237-5","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 5","pages":"307-308"},"PeriodicalIF":25.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-026-01237-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-03-16DOI: 10.1038/s41422-026-01242-8
Adriana E Golding, Raffaella De Pace
{"title":"Mapping brain cell-type-specific diversity of lysosomal proteins.","authors":"Adriana E Golding, Raffaella De Pace","doi":"10.1038/s41422-026-01242-8","DOIUrl":"https://doi.org/10.1038/s41422-026-01242-8","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":25.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466807","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 ResearchPub Date : 2026-03-16DOI: 10.1038/s41422-026-01234-8
Xiaojing Li, Renjie Li, Yiqing Wei, Jiexin Chen, Jiaojiao Zhao, Jun Zhao, Wei Wang, Na Li, Lili Wang, Tuo Hu, Yanli Dong, Yongping Zhu, Chao Wei, Long Li, Wei Zhang, Zhuo Huang, Yan Zhao
{"title":"Assembly and gating mechanism of native AMPA receptors from the cerebellum.","authors":"Xiaojing Li, Renjie Li, Yiqing Wei, Jiexin Chen, Jiaojiao Zhao, Jun Zhao, Wei Wang, Na Li, Lili Wang, Tuo Hu, Yanli Dong, Yongping Zhu, Chao Wei, Long Li, Wei Zhang, Zhuo Huang, Yan Zhao","doi":"10.1038/s41422-026-01234-8","DOIUrl":"https://doi.org/10.1038/s41422-026-01234-8","url":null,"abstract":"<p><p>AMPA receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission throughout the central nervous system. Calcium-permeable AMPARs and GluA4-containing receptors are critical for cerebellar functions, such as motor learning, associative memory, auditory processing, and synaptic plasticity. In contrast to the well-characterized, predominantly GluA2-containing AMPARs of the hippocampus and cortex, cerebellar AMPARs contain a higher proportion of GluA4 and remain poorly understood. Here, we generated a highly GluA4-specific antibody. Using this antibody in combination with antibodies specifically recognizing GluA1 and GluA2, we purified native AMPARs and determined the subunit compositions of both calcium-impermeable and calcium-permeable native AMPARs in the cerebellum. The isolated cerebellar AMPARs that contained both GluA1 and GluA4 were calcium-permeable, with GluA4 occupying mainly the B/D positions, GluA1 occupying the A/C positions, and the complex associated primarily with cornichon 3 (CNIH3). We determined the structures of the complex in distinct functional states, including the resting, active, and desensitized states, and characterized the conformational transitions that underlie its activity. During desensitization, the receptor adopts a pseudo-4-fold configuration of the ligand-binding domain layer, which may be important for its functional properties. This study provides a blueprint for the subunit compositions of AMPARs in the cerebellum and clarifies the gating mechanism of the calcium-permeable native AMPAR<sup>A1A4</sup>-CNIH3 complex, providing significant insight into AMPAR-mediated synaptic transmission in the cerebellum.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":25.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466818","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 ResearchPub Date : 2026-03-16DOI: 10.1038/s41422-026-01238-4
Omar Zabad, Kathrin Maedler
{"title":"To β or not to β: think zinc (again)!","authors":"Omar Zabad, Kathrin Maedler","doi":"10.1038/s41422-026-01238-4","DOIUrl":"10.1038/s41422-026-01238-4","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"36 5","pages":"311-312"},"PeriodicalIF":25.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-026-01238-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-03-04DOI: 10.1038/s41422-026-01227-7
Jiawang Chen, Tao Xu, Chenchen Zhang, Li Li, Yan He, Zhaoxia Sun, Jiasheng He, Zhimo Yao, Peng Cai, Yipeng Huang, Fenfen Ye, Wei Guo, Manli Jia, Jia Qu, Jiang-Fan Chen, Yi Zhang
{"title":"40 Hz light flickering alleviates chronic pain via adenosine signaling in the retina-amygdala pathway","authors":"Jiawang Chen, Tao Xu, Chenchen Zhang, Li Li, Yan He, Zhaoxia Sun, Jiasheng He, Zhimo Yao, Peng Cai, Yipeng Huang, Fenfen Ye, Wei Guo, Manli Jia, Jia Qu, Jiang-Fan Chen, Yi Zhang","doi":"10.1038/s41422-026-01227-7","DOIUrl":"https://doi.org/10.1038/s41422-026-01227-7","url":null,"abstract":"Chronic pain affects over 20% of the global population, yet frontline treatments remain limited in efficacy and are often hampered by serious side effects. In search of novel and effective neuromodulation alternatives, we discovered that 40 Hz flickering light effectively alleviates inflammatory and neuropathic pain in mice. We identified the retina-central amygdala (CeA) pathway as a critical conduit for the analgesic effects of 40 Hz flickering light. Using circuit-specific manipulations, we demonstrated that activation of the retina-CeA pathway is both sufficient to mimic and necessary to mediate the analgesic outcomes of 40 Hz light stimulation. In terms of mechanism, we found that 40 Hz light flickering significantly increases extracellular adenosine levels in the CeA. Local pharmacological blockade of equilibrative nucleoside transporters prevented this adenosine increase and abolished the analgesic effects of 40 Hz light flickering, whereas focal adenosine infusion phenocopied the light-induced analgesia. Both interventions required A2A receptor signaling to suppress nociceptive responses. Furthermore, we found that hyperalgesia could be destabilized in the CeA and reversed by 40 Hz light stimulation or adenosine infusion, mirroring memory reconsolidation processes and implicating the CeA as a key locus for pain memory erasure. Collectively, our findings demonstrate the multifaceted therapeutic benefits of 40 Hz light flickering as a novel non-invasive approach for pain management and reveal a distinct retina-CeA circuit and adenosine signaling mechanism for control of chronic pain and pain memory.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"130 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346818","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}