| Table of Contents |
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| Spatial transcriptomics redraws the olfactory map |
| Per Uhlén |
| Two studies in this issue of Cell, by Bintu et al. and Brann et al., overturn the long-standing zonal model of olfactory receptor organization. Using image-based spatial transcriptomics, they reveal that receptors occupy reproducible positions along continuous gradients, coupling receptor choice to axonal targeting through a shared molecular code. |
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| Autoantibodies in long COVID: A mechanistic foothold in a heterogeneous disease |
| Emma C. Wall, Alex G. Richter |
| Long COVID is a heterogeneous, multi-system disease that poses challenges for patients, health systems, and economies. Two papers in Cell and Cell Reports Medicine from independent groups suggest that autoantibodies in a subset of long COVID patients can directly drive symptoms such as pain, fatigue, or neurocognitive problems. |
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| B cells just got a workout |
| Maria E. Moreno-Fernandez, Senad Divanovic |
| In this issue of Cell, Mao et al. reveal that B cells play an unexpected, immune-independent role in exercise physiology by facilitating multi-organ communication. Secreting TGF-β1, they transcriptionally reprogram hepatic glutamine metabolism via GLS2 and SLC7A5, preserving skeletal muscle glutamate levels, which sustain mitochondrial function, Ca2⁺ signaling, and ATP production, enhancing exercise capacity. |
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| Mesenchymal drift: A convergent framework for the hallmarks of aging |
| Jinlong Y. Lu, William B. Tu, Shuai Ma, Zaijun Ma, Ivan Imaz-Rosshandler, Mingxi Weng, Jing Qu, Concepcion Rodriguez Esteban, Pradeep Reddy, Guang-Hui Liu, Juan Carlos Izpisua Belmonte |
| Aging is marked by a systemic loss of tissue homeostasis. This review focuses on mesenchymal drift, where cells progressively lose lineage identity and acquire mesenchymal traits, as a convergent framework that integrates and fuels the hallmarks of aging, forming a potentially targetable molecular network to restore identity and counter multiple age-related pathologies. |
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| A causal link between autoantibodies and neurological symptoms in long COVID |
| Keyla Santos Guedes de Sá, Julio Silva, Rafael Bayarri-Olmos, Christopher A. Baker, Zhenni Lu, Wilson Gipson, Daxiang Na, Bandy Chen, Li Wenxue, Delyar Khosroabadi, Ryan Brinda, Robert Alec Rath Constable, Britney Omene, Patricia A. Colom Díaz, Dong-il Kwon, Gisele Rodrigues, Harald Heidecke, Kai Schulze-Forster, Amanda Gross, Tom Shneer, Amanda Clarke, Thomas Linnekin, Ashley Brate, Lev Brown, Henry Buda, Shashi Jatiani, Lenny Moise, Kerrie Greene, Sachin Bhagchandani, Bornali Bhattacharjee, Jeffrey Gehlhausen, Jamie Wood, Laura Tabacof, Carmen Scheibenbogen, Yansheng Liu, Leying Guan, Marc Schneeberger Pane, David Putrino, Tamas L. Horvath, Akiko Iwasaki |
| Passive transfer of IgG from long COVID patients induces pain behavior accompanied by intraepidermal nerve fiber damage in mice. |
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| Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections |
| Morgane Fournier, Matthias Vanderkerken, Karim Dorgham, Paul Bastard, Olivia Ahouzi, Stephane Duquerroy, Ngoc Khanh Nguyen, Manon Broutin, Manon Charlet, Alexis Vandenberghe, Paolo Van Endert, Lucy Bizien, Omaira Da Mata-Jardin, Andrés Ferriño-Iriarte, Ahmed Haouz, Thibaut Belmondo, Sophie Hüe, Alessandro Borghesi, Carlos Rodríguez-Gallego, Donald C. Vinh, Evangelos Andreakos, Filomeen Haerynck, Rabih Halwani, Qiang Pan-Hammarström, Niklas K. Björkström, Benedikt Strunz, Trine H. Mogensen, Antonio Piralla, Stefania Varchetta, Jorge Freixinet, Lucie Roussel, Sophie Trouillet Assant, Bénédicte Neven, Romain Levy, Tom le Voyer, Ottavia M. Delmonte, Cliona O’Farrelly, Jacques Rivière, Blanca Amador Borrero, Amélie Servettaz, Roger D. Kouyos, Daniel E. Kaufmann, Etienne Crickx, Marc Michel, Anne Puel, Laurent Abel, Charles-Edouard Luyt, Alexis Mathian, Kai Kisand, Darragh Duffy, Lluis Quintana-Murci, Zahir Amoura, Benjamin G. Hale, Jean-Claude Weill, Jean-Laurent Casanova, Felix A. Rey, Guy Gorochov, Pascal Chappert, Matthieu Mahévas |
| By integrating functional and structural approaches with AI-based analysis of autoantibodies against type-I IFNs, these neutralizing autoantibodies—linked to severe viral diseases in humans—are shown to arise from pre-existing autoimmunity driven by prolonged germinal center affinity maturation. |
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| B cell deficiency limits exercise capacity by remodeling liver glutamate metabolism |
| Youxiang Mao, Ziyan Xia, Xu Pan, Wenjun Xia, Peng Jiang |
| B cells regulate exercise capacity through immune-independent liver-muscle metabolic signaling, and B cell deficiency limits muscle performance. Mechanistically, B cell-secreted TGF-β1 increases hepatic glutamine-to-glutamate conversion, raising glutamate in blood and muscle. This promotes muscle calcium signaling and mitochondrial function, positively regulating exercise capacity. |
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| Hyperinnervation inhibits organ-level regeneration in mammalian skin |
| Hannah T. Tam, Jingyu Peng, Rebecca Freeman, Yulia Shwartz, Shlomi Brielle, Sakshi Garg, Siti Rahmayanti, Stephen J. Crocker, Devin Coon, Ya-Chieh Hsu |
| Open Access |
| Embryonic skin wounds regenerate diverse cell types across all lineages, but this capacity is lost soon after birth, as a postnatal wound-specific fibroblast population drives excessive innervation that blocks regeneration. Reducing hyperinnervation at the injury site restores regenerative potential across lineages after postnatal wounding. |
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| Unbiased niche labeling maps immune-excluded niche in bone metastasis |
| Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L. Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G. Edwards, Hilda L. Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L. Satcher, Xiang H.-F. Zhang |
| An unbiased niche-labeling method, SAMENT, maps cellular and molecular features of metastatic niches and highlights the role of ERα⁺ niche macrophages in preventing T cell infiltration, thereby promoting bone metastasis. |
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| Streptomyces enrichment in roots during drought is uncoupled from plant benefit and is driven by host suppression of iron uptake and immunity |
| Connor R. Fitzpatrick, Ryker Allen Smith, Junko Hige, Theresa F. Law, Dor Russ, Oluwadamilola Elizabeth Ajayi, Abdul Aziz Eida, Pierre Jacob, Monet Jowers, Narender Kumar, Cindy Thao Uyen Lai, Manuel Anguita-Maeso, S. Brook Peterson, Chinmay Saha, Tara Skelly, Qinqin Zhao, Wenbin Zhou, Sarah R. Grant, Joseph D. Mougous, Corbin D. Jones, Jeffery L. Dangl |
| Drought drives Streptomyces enrichment in roots, not by a plant “cry for help” but via the triggering of host immunity suppression and iron uptake, where intra-genus interactions dictate strain-level outcomes, including growth benefits. |
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| Predicting competition and substrate preferences for targeted microbiome alteration |
| Oriane Moyne, Grant J. Norton, Mahmoud Al-Bassam, Chloe Lieng, Deepan Thiruppathy, Manish Kumar, Eli Haddad, Yuhan Weng, Manuela Raffatellu, Livia S. Zaramela, Karsten Zengler |
| Translation profiling reveals how microbes allocate cellular resources in complex communities. The microbial interaction and niche determination (MIND) framework links functional prioritization to competition and substrate preferences, enabling the rational design of targeted prebiotic and probiotic interventions to selectively manipulate microbiomes across environmental and host-associated systems. |
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| Multi-cohort proteogenomic analyses reveal genetic effects across the proteome and diseasome |
| Mine Koprulu, Karl Smith-Byrne, Brian Richard Ferolito, Erin Macdonald-Dunlop, Jian’an Luan, Åsa K. Hedman, Chibuzor Franklin Ogamba, Jurgis Kuliesius, Linda Repetto, Anna Ramisch, Fahim Abbasi, Johan Ärnlöv, Themistocles L. Assimes, Hanna M. Björck, Sophia Björkander, Morten Böttcher, Adam Stuart Butterworth, Zhengming Chen, Kelly Cho, Robert Joseph Clarke, Simon Riddington Cox, Kamila Czene, John Danesh, George Dedoussis, Sölve Elmståhl, Niclas Eriksson, Per Eriksson, Tõnu Esko, Aida Ferreiro-Iglesias, Paul William Franks, Jingyuan Fu, J. Michael Gaziano, Mohsen Ghanbari, Christian Gieger, Arthur Gilly, Harald Grallert, Marc James Gunter, Stefan Gustafsson, Andreas Göteson, Per Frans Leonard Hall, Oskar Hansson, Sarah Elizabeth Harris, Caroline Hayward, Christian Herder, Natalia Hernandez-Pacheco, Ziad Hijazi, Robert F. Hillary, Jemma Caroline Hopewell, Shixian Hu, Shih-Jen Hwang, Christina Jern, Åsa Johansson, Lina Jonsson, Anette Kalnapenkis, Nicola Dorothy Kerrison, Pik Fang Kho, Lucija Klaric, Leonhard Kohleick, Julia Kraft, Mikael Landén, Daniel Levy, Liming Li, Lars Lind, Jirong Long, Niklas Mattsson-Carlgren, Erik Melén, Simon Kebede Merid, Philipp Mertins, Karl Michaëlsson, Peter Loof Møller, Federico Murgia, Mette Nyegaard, Young-Chan Park, Ewan Pearson, James Peters, John Ross Petrie, Grace Png, Ozren Polašek, Bram Peter Prins, Stephan Ripke, Michael Roden, Palle Duun Rohde, Saredo Said, Xia Shen, Jochen M. Schwenk, Agneta Siegbahn, J. Gustav Smith, Tara M. Stanne, Karsten Suhre, Johan Sundström, Barbara Thorand, Elsa Valdes-Marquez, Costanza L. Vallerga, Joyce B.J. van Meurs, Ana Viñuela, Urmo Võsa, Lars Wallentin, Robin G. Walters, Nicholas John Wareham, Joachim Eduard Weber, Rinse Karel Weersma, James F. Wilson, Simon Winther, Summaira Yasmeen, Daniela Zanetti, Eleftheria Zeggini, Jing Hua Zhao, Alexandra Zhernakova, Daria V. Zhernakova, Matthias Ziehm, Benedikt Mathias Kessler, Alexandre C. Pereira, Anders Mälarstig, Maik Pietzner, Claudia Langenberg |
| Open Access |
| A large-scale multi-cohort proteogenomic study identifies genetic loci influencing circulating protein levels, revealing pathways and cell types that regulate the circulating proteome and highlighting disease insights and evidence for potential therapeutic opportunities. |
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| A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain |
| David H. Brann, Tatsuya Tsukahara, Cyrus Tau, Dennis Kalloor, Rylin Lubash, Lakshanyaa Thamarai Kannan, Nell Klimpert, Mihaly Kollo, Martín Escamilla-Del-Arenal, Bogdan Bintu, Andreas Schaefer, Alexander Fleischmann, Thomas Bozza, Sandeep Robert Datta |
| Open Access |
| Dorsoventral epithelial position induces graded expression of a transcriptional program that maps each of the 1,100 olfactory sensory neuron subtypes to stereotyped spatial distributions in the epithelium, thereby building a precise receptor map in the nose that aligns with the glomerular map in the olfactory bulb. |
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| Nuclear envelope budding enables export of large transcripts in muscle cells |
| Sofia Zaganelli, Janet B. Meehl, Robert G. Abrisch, Gia K. Voeltz |
| Open Access |
| During myogenesis, inner nuclear membrane buds export extremely long sarcomeric transcripts. UIF controls RNA cargo targeting into these buds, and ESCRT-III remodeling is required to internalize UIF and its cargo, revealing a non-canonical pathway for exporting large transcripts. |
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| ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging |
| Kaibo Ma, Xiaojie Ma, João F. Shida, Zijian Niu, Yuzhu Karlie Lin, Saptarshi Mandal, Alexandra Dobbins, Lior Golomb, Michael J. Eck, Heidi Greulich, Matthew Meyerson, Chunte Sam Peng |
| Open Access |
| Ma et al. developed long-term single-particle tracking of ErbB family receptors in living cells using upconverting nanoparticles. They discovered constitutive HER2 and HER3 homodimerization and showed how oncogenic mutations and ligand stimulation affect dimerization dynamics, offering new insights into the mechanisms of oncogenic signaling and the ErbB receptor interaction network. |
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| Rational design of Gi-biased CB1 agonist with reduced side effects |
| Yu-Ying Liao, Jinxin Che, Yun-Tao Gao, Jianheng Xue, Linjie Li, Lin-Lin Wu, Jia-Xue Hu, Meng-Ting Hu, Linghua Xie, Huibing Zhang, Dan-Dan Shen, Yingjun Dong, Shaokun Zang, Na Zhang, Hao Wang, Yan Zhang, Xiaowu Dong, Xiao-Ming Li |
| Rational design of cannabinoid receptor agonists that uncouple therapeutic analgesia from unwanted on-target effects, establishing a blueprint for next-generation non-opioid therapeutics. |
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| Rational discovery of therapeutic PAK1 allosteric activators |
| Yu He, James S.H. Bae, Elżbieta Nowak, Carlos Outeiral, Daniel A. Nissley, Anthony Tumber, Georgina Berridge, Eidarus Salah, Yi Wang, Wenqi He, Hongyuan Zhang, Tangting Chen, Samuel Tusk, Sebastian Mathea, Ying-Jie Wang, Alexander Grassam-Rowe, Philipp Kukura, Christopher J. Schofield, Darragh P. O’Brien, Andrea Pierangelini, Grant C. Churchill, Thomas Lanyon-Hogg, Yunbo Ke, Chao Xu, Tao Ye, Hugh Watkins, Liming Ying, Andreas Koschinski, R. John Solaro, Xiaoqiu Tan, Jani R. Bolla, Xin Wang, Stefan Knapp, Charlotte M. Deane, Manuela Zaccolo, Marcin Nowotny, Ming Lei |
| Open Access |
| Kinase activators are difficult to develop despite their therapeutic promise. Here, we report the discovery of small-molecule p21-activated kinase 1 (PAK1) allosteric activators using a rational, peptide-guided strategy targeting the autoinhibitory mechanism. These compounds exhibit therapeutic efficacy in hypertrophic cardiomyopathy, underscoring the potential of this strategy for therapeutic kinase activator discovery. |
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| Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression |
| Junyeop Kim, Yerim Hwang, Sumin Kim, Daeyeol Kwon, Jeonghyun Park, Byounggook Cho, Saemin An, Soi Kang, Yunkyung Kim, Seonghun Kim, Christopher J. Lengner, Soochan Kim, Youngeun Kwon, Jung-Suk Sung, Jongpil Kim |
| The EMF-inducible gene switch (Ei) platform provides precise spatiotemporal control of gene expression through Cyb5b-mediated calcium oscillations. This system enables Ei-OSK-driven in vivo rejuvenation reprogramming, Ei-mutant APP expression in the context of Alzheimer’s disease, and behavioral rescue in depression through Ei-Tph2-mediated neuromodulation. |
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| Whole-body molecular and cellular mapping of the laboratory mouse |
| Margarette H. Clevenger, Denis Cipurko, Ashwini Patil, Bohan Li, Michihiro Takahama, Linghan Mei, Madison Plaster, Gabriella Richey, Tadafumi Kawamoto, Feng Bao, Nicolas Chevrier |
| Open Access |
| A scalable experimental and computational platform for mapping all organs and cell types in the mouse body, enabling comprehensive analysis of tissue organization and disease responses. |
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| Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson’s disease models |
| Shiwei Du, Qi Long, Yanshuang Zhou, Jiangqin Fu, Hao Wu, Liang Yang, Yaohang Xie, Yingzhe Ding, Maolei Zhang, Jingyi Guo, Mengfei Wang, Jiajun Lin, Mingli Hu, Jian Zhang, Deyang Yao, Wei Li, Feixiang Bao, Ge Xiang, Yi Wu, Yile Huang, Haozhao Liang, Rui Wang, Heying Li, Baodan Chen, Chong Li, Junwei Wang, Jiwei Zhang, Dajiang Qin, Jianwei Sun, Yun Zhu, Fei Sun, Wuming Wang, Gang Lu, Wai-Yee Chan, Hui Zhao, Chenli Liu, Xingguo Liu |
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