Excited to share our new review: “The landscape of single-cell foundation models: design principles, applications, and open challenges” This work brings together collaborators from 23 institutions, including Stanford University, Gladstone Institutes, University of California, San Francisco, Helmholtz Munich, Massachusetts Institute of Technology, and Yale University. The field has moved incredibly fast—from scBERT in 2021, geneformer in 2022 to more than 100 foundation models today spanning transcriptomics, epigenomics, spatial omics, multimodal biology, and LLM-integrated frameworks. But this rapid growth has also created real confusion, for example: • Which tokenization strategy should we use? • Do conventional scaling laws apply to biological systems? • Why does perturbation prediction remain stubbornly difficult? • And how should we evaluate whether a model has learned meaningful biology rather than dataset-specific patterns? ... We were among the early groups working on single-cell foundation models, beginning in 2022 as the field was taking shape. Our journey has included: • CellPLM (ICLR 2024), an early model for learning cellular states in their multicellular context • scLinguist, a Hyena-based multimodal model for RNA-to-protein translation • Tabula (NeurIPS 2025; extended version under review at Nature Portfolio), a privacy-preserving predictive model combining tabular and federated learning to study gene regulation and aging Building these models gave us a firsthand view of both the field’s promise and its unresolved challenges: biological fidelity, generalization, multimodality, perturbation modeling, evaluation, and privacy. Those experiences motivated this review. We hope this review as a structured guide for both computational scientists and experimental biologists—covering how these models are built, where they genuinely enable biological discovery, including experimentally validated therapeutic targets, and where the most important gaps remain. 📄 Paper: lnkd.in/gSxJBEwt 📚 Curated paper list: lnkd.in/gU4R4Rt3 Deeply grateful to all of our co-authors and collaborators—this was a true community effort. @shiyu_jiang23 , Zhaoyu Fang, Yujie Zhang, @xutzhang , @jkobject , Weixu Wang, @alexanderfuxi , Aakash Patel, Syed Rizvi, @Y_Ryan_Lu , @SiyuHe7 , @YixinxinWang , @KejunYing , @peterpaohuang , @YifanLu2024 , @Nanguage , Mengchen Wang, Ziyang Miao, Jianhui Lin, Jimmy Ding, Jerry Wang, @imweio , @TianlongChen4 , Guoxian Yu, Min Li, Jiayi Ma, @feiwang03 , @Yuyingxie , @tangjiliang , @raulrabadan , @david_van_dijk , @cmuptx , @PengHeAtlas , Emily B. Fox, @dasongle , @fabian_theis , @ericxing , Christina Theodoris, @Xiaojie_Qiu #SingleCell #FoundationModels #ComputationalBiology #Genomics #AIForScience #SpatialOmics #PerturbationBiology