Cell: March 19, 2026 (Volume 189, Issue 6)

[Virtual Post Bioclues]

 

 

Mar 19, 2026 Vol. 189, Iss. 6 Website Table of Contents Online Now Archive Highlights Announcements Read the first papers from Cell Press Blue Research with infinite potential across life, physical, medical, sustainability, and applied sciences The world needs science that inspires Cell Press is committed to serving the scientific community, so that every paper we publish makes an impact. Cell Symposia: Biological function in 3D: Structure, dynamics, and AI November 5-7, 2026 | Shenzhen, China Cell Symposia: Hallmarks of aging October 4-6, 2026 | Seville, Spain Featured content RNA modifications in gene regulation: Functions and pathways Wei et al. Divergent tumor immunity determined by bacteria-cancer cell engagement Yao et al. Online now Controlled human influenza infection reveals heterogeneous expulsion of infectious virus into air Vargas-Maldonado et al. Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles Geng et al. Table of Contents Leading Edge Review RNA modifications in gene regulation: Functions and pathways Jiangbo Wei, Chuan He Articles LUMI-lab: A foundation model-driven autonomous platform enabling discovery of ionizable lipid designs for mRNA delivery Yue Xu, Haotian Cui, Kuan Pang, Gen Li, Fanglin Gong, Songtao Dong, Bo Wang, Bowen Li LUMI lab is a foundation model-driven self-driving platform that autonomously discovers ionizable lipids for mRNA delivery. Iterative active learning uncovered brominated tails as a potent structural motif that enables efficient and safe pulmonary mRNA delivery. Light-directed evolution of dynamic, multi-state, and computational protein functionalities Vojislav Gligorovski, Marco Labagnara, Lorenzo Scutteri, Marius Blackholm, Andreas Möglich, Nahal Mansouri, Sahand Jamal Rahi Open Access Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protein behaviors that were previously difficult to evolve. Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy Annika Zink, Dao-Fu Dai, Annika Wittich, Marie-Thérèse Henke, Giulia Pedrotti, Sonja Heiduschka, Guillem Santamaria, Tancredi Massimo Pentimalli, Christian Brueser, Sofia Notopoulou, Abdul Rahim Umar, Aleksandra Zhaivoron, Laura Petersilie, Caleb Jerred, Jesper Bergmans, Louis Anton Neu, Fabian Schumacher, Jan Keller-Findeisen, Agnieszka Rybak-Wolf, Daniel Stach, Jeanette Reinshagen, Undine Haferkamp, Kim Krieg, Andrea Zaliani, Liliya Euro, Alessia Di Donfrancesco, Chiara Santanatoglia, Enrica Cappellozza, Marta Suarez Cubero, Mario Pavez-Giani, Oleh Bakumenko, David Meierhofer, Alan Foley, Susanne Morales-Gonzalez, Isabella Tolle, Diran Herebian, Daniele Bonesso, Giulia Cecchetto, Sakurako Nagumo Wong, Monica Moresco, Alessandra Maresca, Ilaria Decimo, Francesco De Sanctis, Annalisa Adamo, Merel J.W. Adjobo-Hermans, Roberto Duchi, Maria Barandalla, Marco Scaglia, Andrea Perota, Cesare Galli, Burkhard Kleuser, Lukas Cyganek, Chris Mühlhausen, Lars Schlotawa, Valeria Tiranti, Ertan Mayatepek, Ildiko Szabo, Chiara La Morgia, Thomas Klopstock, Valerio Carelli, Felix Distelmaier, Andrea Rossi, Nikolaus Rajewsky, Ghanim Ullah, Stefan Jakobs, Christine R. Rose, Spyros Petrakis, Frank Edenhofer, Werner J.H. Koopman, Pawel Lisowski, Anu Suomalainen, Dario Brunetti, Antonio del Sol, Emanuela Bottani, Ole Pless, Markus Schuelke, Alessandro Prigione Open Access Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome. Tuning the sensitivity of mechanosensory receptors through histidine scanning Yuanhao Wang, Yuhan Wang, Wenjie Yuan, Mingyu Fan, Xiaojing Wang, Anhui Wang, Yanling Bao, Yajing Zhang, Jia Chi Tan, Jianglai Wang, Junshuang Liu, Tianqi Huang, Zixuan Han, Biling Pei, Lijuan Chen, Zhengxu Ren, Xueqing Wang, Lanxin Hu, Siqi Wu, Mengke Pang, Sifan Wang, Zihuan Yang, Jiaze Li, Delian Huang, Shuai Shao, Huairui Yuan, Ling Wu, Yinnian Feng, Penghui Zhou, Guohui Li, Bo Sun, Chenqi Xu, Nicholas R.J. Gascoigne, Xiang Zhao Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism. β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer Shan Liu, Puneeth Guruprasad, Ranjani Ramasubramanian, Bhoomi Madhu, Luca Paruzzo, Kecheng Han, Andre Kelly, Alexander Shestov, He N. Xu, Alberto Carturan, Chaoting Zhou, Kevin R. Amses, Amichay Afriat, Lev Litichevskiy, Jason Lin, Ezra Dubowitz, Neil Tangal, Jing Zhang, Alana McSween, Melody Tan, Federico Stella, Andrew Lee, Siena Nason, Xianxin Hua, Michael Schneider, Madeleine Sleeman, Yunlin Zhang, Giulia Gabrielli, Ziqi Yang, Raymone Pajarillo, Ruchi Patel, Guido Ghilardi, Vrutti Patel, Akshita Joshi, Shunzhou Jiang, Yanqing Jiang, Patrizia Porazzi, Julia C. Tchou, Brian Keith, Mingyao Li, Elise Chong, Stephen J. Schuster, Michael Milone, Joshua Rabinowitz, Roddy S. O’Connor, Christoph A. Thaiss, Maayan Levy, Marco Ruella β-hydroxybutyrate (BHB), the ketone body associated with a ketogenic diet, metabolically reprograms and fuels CAR T cells to achieve proliferation, cytokine production, and superior tumor control. These findings suggest that BHB supplementation may be a practical way to boost adoptive cancer immunotherapy. Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition Matthew L. Miller, Timothy J. Thauland, Smriti Sameer Nagarajan, Wenqi Ellen Zuo, Miguel A. Moreno Lastre, Manish J. Butte Equipping T cells with fungal enzymes to utilize cellobiose (a safe and natural disaccharide of glucose obtained from the wood polymer cellulose) enhances their viability and effector function in tumor microenvironments where glucose concentrations are constrained. Extracellular matrix sensing regulates intratumoral heterogeneity of autophagic flux Mohamad Assi, Ruohong Wang, Emily A. Kawaler, Albert S.W. Sohn, M. Zahidunnabi Dewan, Despoina Kalfakakou, Joel Encarnacion-Rosado, Kevin S. Kapner, Koelina Ganguly, Joao A. Paulo, Diane M. Simeone, Andrew J. Aguirre, Robert S. Banh, Alec C. Kimmelman Human pancreatic cancer cells sense specific components of the ECM to fine-tune their autophagy flux levels, conferring the ability to coordinate proliferation, survival, and responsiveness to chemotherapy. Targeting ECM sensing may turn this ability into a therapeutic opportunity. Divergent tumor immunity determined by bacteria-cancer cell engagement Bingqing Yao, Xiaoqin Liu, Kanghui Ruan, Xiunan Fang, Chuhan Jiang, Weixiang Bian, Yajing Guo, Xiaosheng Zhu, Zebin Shang, Tianen Hu, Pei Cai, Meizhen Lin, Chunhui Wang, Xiaoyu Kuang, Fanglin Luo, Zhanhao Zhang, Shang Li, Jia Yao, Xu Li, Shang Cai In a preclinical breast cancer metastasis model, the same bacteria strain, when present intracellularly versus extracellularly, exerts opposing effects on tumor immunity by inducing divergent neutrophil states, highlighting the intricacy in bacterial-host engagement for shaping tumor immunity. Hijacking ERAD for targeted degradation of transmembrane proteins Haikun Song, Wei Wang, Tingfang Mei, Huiwen Zheng, Keni Ning, Xiaofan Liu, Siulam Cheung, Zhiyuan Cao, Danqi Sheng, Xiaohan Mai, Haoran Zhu, Guankai Guo, Shuaimeng Liu, Rongkai Wei, Qian Wang, Yu Cao, Yu Ding, Yiyan Fei, Rui Liu, Motoyuki Hattori, Chunquan Sheng, Boxun Lu Development of an ERAD-hijacking technology overcomes the challenges of current targeted protein degradation approaches to achieve degradation of transmembrane proteins. A circadian rheostat drives proton electrochemical gradients to optimize cell-type-specific growth in Arabidopsis Lu Xiong, Motohide Seki, Akiko Satake, Paloma Mas Open Access The clock component CCA1 functions as a molecular rheostat, fine-tuning cell-type-specific electrochemical gradients to optimize carbon allocation and the timely coordination of shoot and root growth balance. Human-specific features of the cerebellum and ZP2-regulated synapse development Suel-Kee Kim, Adriana Cherskov, Aastha Sindhwani, Sang-Hun Choi, Hyojin Kim, Ming-Li Li, Menglei Zhang, Xoel Mato-Blanco, Yuting Liu, Nicola Micali, David M. Young, Mark Estacion, Yueqi Zhang, José Manuel Ruiz-Jiménez, Anandita Nadkarni, Victor Luria, Suvimal Kumar Sindhu, Ipsita Chatterjee, Akemi Shibata, Dan Liang, Hyesun Cho, Saejeong Park, Ana Spajic, Rothem Kovner, Martina Glavan, Rachel J. Chen, Ryan D. Risgaard, Xinyun Li, Sirisha Pochareddy, Amir Karger, Anita Huttner, Yury M. Morozov, Etienne W. Daadi, Carlo Colantuoni, Kevin T. Gobeske, John J. Ely, Patrick R. Hof, Marcel M. Daadi, Chet C. Sherwood, Alvaro Duque, Shaojie Ma, Andre M.M. Sousa, Stephen G. Waxman, Pasko Rakic, Gabriel Santpere, Stephan J. Sanders, Nenad Sestan Open Access Human-specific transcriptomic and regulatory features are present in the cerebellum, with ZP2 playing a key role in synapse regulation. ZP2 expression is induced by pontine mossy fibers, leading to decreased synaptic proteins and neuronal activity, which provides insights into the evolutionary development of the human cerebellum. Resources Molecular architecture of human dermal sleeping nociceptors Jannis Körner, Derek Howard, Hans Jürgen Solinski, Marisol Mancilla Moreno, Natja Haag, Andrea Fiebig, Anna Maxion, Shamsuddin A. Bhuiyan, Idil Toklucu, Raya A. Bott, Ishwarya Sankaranarayanan, Diana Tavares-Ferreira, Stephanie Shiers, Nikhil N. Inturi, Esther Eberhardt, Lisa Ernst, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Marc D. Beyer, Thomas Stiehl, William Renthal, Ingo Kurth, Jenny Tigerholm, Jordi Serra, Theodore J. Price, Martin Schmelz, Barbara Namer, Shreejoy Tripathy, Angelika Lampert Open Access Integration of electrophysiology with single-cell transcriptomics defines the molecular signature of human dermal sleeping nociceptors and reveals oncostatin M as a selective modulator of these neurons in humans, providing a therapeutic entry point for neuropathic pain. Whole-organ and whole-body 3D atlases enable cellome-wide profiling Shota Y. Yoshida, Katsuhiko Matsumoto, Satoshi Takagi, Fukuaki L. Kinoshita, Katsunari Yamashita, Daichi Shigeta, Yoshichika Yoshioka, Tetsuo Ushiku, Eiichi Morii, Etsuo A. Susaki, Hiroki R. Ueda Whole-organ and whole-body atlases at single-cell resolution enable quantitative cellome-wide analysis across development, physiology, and pathology. Genomic atlas of Bifidobacterium infantis and B. longum informs infant probiotic design Yan Shao, Shuyi Wang, Bonface M. Gichuki, Mark D. Stares, Timothy J. Rozday, Nitin Kumar, Hilary P. Browne, Nicholas J.R. Dawson, James M. Njunge, Caroline Tigoi, Narshion Ngao, Mohammod Jobayer Chisti, Benson O. Singa, Samuel Kariuki, Abdoulaye Hama Diallo, Ali Faisal Saleem, Syed Asad Ali, Ezekiel Mupere, Emmie Mbale, Kirkby D. Tickell, Wieger P. Voskuijl, Christina L. Lancioni, Robert H.J. Bandsma, Tahmeed Ahmed, Judd L. Walson, James A. Berkley, Trevor D. Lawley Open Access A global genomic survey of infant gut bifidobacteria shows that B. infantis remains highly prevalent and diverse in infants from low- and middle-income countries but scarce in Western, industrialized populations and poorly represented in current probiotics. This genomic and culture collection catalogs geo-specific B. infantis strains and provides a blueprint for developing probiotics tailored to local diets and populations to support infant health.