Cell Reports Methods: March 2026 (Volume 6, Issue 3)

[Virtual Post Bioclues]

 

Mar 23, 2026 Vol. 6, Iss. 3 Open Access Website Table of Contents Online Now Archive Highlights Announcements Collection: Metabolism New papers are added as they are published. Explore this Cell Reports Methods collection. In the news: Human nasal passages defend against the common cold and help determine how sick we get Recent Cell Press Blue research covered in The Washington Post, The Scientist, CNN, and more. The world needs science that inspires Cell Press is committed to serving the scientific community, so that every paper we publish makes an impact. Meet with a Cell Reports Methods editor external link opens in new window Our editors are available to chat! Book a virtual meeting with them to discuss your research. Table of Contents Review Advances and applications of organ-on-a-chip technology Jeong Sik Kong, Jisoo Kim, Jinah Jang, Dong-Woo Cho Organ-on-a-chip technology recreates key structural and functional features of human organs within microfluidic platforms, providing physiologically relevant alternatives to conventional models. In this review, Kong et al. summarize the various fabrication and cultivation strategies and discuss their applications ranging from biosensors, drug testing, and disease modeling to space biology. Reports CBLN2 promoter enables genetic access to wide-field neurons of the tree shrew superior colliculus Arda Kipcak, Alev Erisir Kipcak and Erisir use CBLN2-promoter-based AAVs to access wide-field (WF) neurons of the SC in a pre-primate species, the tree shrew, as well as in the mouse. Using intersectional genetics, they demonstrate that tree shrew WF neurons receive retinal and cortical excitatory inputs preferentially at distal or proximal dendrites in the SC. A genetic strategy for targeting local astrocytes in adult Drosophila Joana Dopp, Sarah Martens, Frederik Hobin, Sofia Mastroianni, Jiekun Yan, Lisa van Ninhuys, Azhar Mauletkhan, Sha Liu Dopp et al. optimized a genetic tool to target local astrocytes in adult Drosophila. They find that labeling efficiency depends on synaptic density. Using this tool, they show that astrocytes bridge the mushroom body and ellipsoid body, two brain centers that lack direct neuronal connections. MitoTracker transfers from astrocytes to neurons independently of mitochondria Katriona L. Hole, Rosalind Norkett, Emma Russell, Patrick Cottilli, Molly Strom, Jack H. Howden, Nicola J. Corbett, Janet Brownlees, Michael J. Devine The mitochondrial dye MitoTracker is commonly used to investigate intercellular mitochondrial transfer (IMT), particularly between astrocytes and neurons. Hole et al. compare MitoTracker with a genetically encoded mitochondrial fluorophore and demonstrate that MitoTracker can transfer from astrocytes to neurons in the absence of mitochondrial transfer, without requiring cell contact. Rapid expansion of primary human vocal fold epithelial cells via targeted pathway inhibition and anchorage-independent sphere culture Xudong Shi, Ryo Suzuki, Haiyan Lu, Hua Zhang, Lingjun Li, Nathan V. Welham Shi et al. report improved primary culture of human vocal fold epithelial cells by using a small-molecule inhibitor cocktail that targets TGF-β, ROCK, and Notch signaling and by employing a free-floating sphere-formation technique. These complementary methods enable rapid population expansion and progenitor enrichment for research and translational applications. Metapipeline-DNA: A comprehensive germline and somatic genomics Nextflow pipeline Yash Patel, Chenghao Zhu, Takafumi N. Yamaguchi, Nicholas K. Wang, Nicholas Wiltsie, Nicole Zeltser, Alfredo E. Gonzalez, Helena K. Winata, Yu Pan, Mohammed Faizal Eeman Mootor, Timothy Sanders, Sorel T. Fitz-Gibbon, Cyriac Kandoth, Julie Livingstone, Lydia Y. Liu, Benjamin Carlin, Aaron Holmes, Jieun Oh, John Sahrmann, Shu Tao, Stefan Eng, Rupert Hugh-White, Kiarod Pashminehazar, Arpi Beshlikyan, Madison Jordan, Selina Wu, Mao Tian, Jaron Arbet, Beth Neilsen, Roni Haas, Yuan Zhe Bugh, Gina Kim, Joseph Salmingo, Wenshu Zhang, Aakarsh Anand, Edward Hwang, Anna Neiman-Golden, Philippa Steinberg, Wenyan Zhao, Prateek Anand, Raag Agrawal, Brandon L. Tsai, Paul C. Boutros Patel et al. develop an automated, extensible, and cloud-compatible DNA sequencing analysis pipeline for DNA sequencing data to transform raw sequencing reads into genetic characteristics and evolutionary features. They demonstrate and validate the pipeline using whole-genome and targeted sequencing data from normal and tumor samples. Articles A robust method for on-chip production and manipulation of lipid vesicles by inverted emulsion Naresh Yandrapalli, David T. Gonzales, Weihua Leng, Cynthia Alsayyah, Nurzhan Abdukarimov, Robert Ernst, T.-Y. Dora Tang Yandrapalli et al. present an on-chip inverted emulsion method that integrates vesicle production, manipulation, and analysis in one platform without the removal of vesicles through the oil layer. This approach reduces vesicle contamination and loss while enabling diverse biochemical assays, thereby lowering the barriers for synthetic cell and membrane research. Convpaint—Interactive pixel classification using pretrained neural networks Lucien Hinderling, Roman Schwob, Guillaume Witz, Ana Stojiljković, Maciej Dobrzyński, Mykhailo Vladymyrov, Joël Frei, Benjamin Grädel, Agne Frismantiene, Olivier Pertz Hinderling et al. present Convpaint, a napari plugin that repurposes pretrained deep learning models for interactive pixel classification. By combining convolutional neural networks and vision transformers with fast machine learning classifiers, Convpaint enables accurate segmentation across diverse imaging modalities with minimal annotations and rapid training times. Practical AI-based cell extraction and spatial statistics for large 3D bone marrow tissue images George Adams, Floriane S. Tissot, Chang Liu, Cera Mai, Chris Brunsdon, Ken R. Duffy, Cristina Lo Celso Adams et al. develop PACESS, a method for generating and analyzing large 3D bone marrow sections. PACESS uses neural networks and spatial statistical approaches to classify hundreds of thousands of cells and reveal cellular relationships in bone marrow. Projection targeting with phototagging to study the structure and function of retinal ganglion cells Martin O. Bohlen, Andra M. Rudzite, Tierney B. Daw, Genevieve M. Kuczewski, Ergi Spiro, Cassie Hammond, Darienne R. Rogers, Alejandro Gallego-Ortega, Michael B. Manookin, Suva Roy, Kimberly Ritola, Marc A. Sommer, Greg D. Field Bohlen et al. introduce a viral-based “projection targeting with phototagging” method that links retinal cell activity, structure, and brain connectivity without relying on genetic models. By tracing visual signals from the eye to the brain’s attention center, this versatile approach advances cross-species studies of vision and attention disorders. A streamlined, nanopore-compatible 5PSeq protocol for rapid phenotypic antimicrobial sensitivity testing Honglian Liu, Susanne Huch, Ryan Hull, Fabricio Romero Garcia, Lilit Nersisyan, Xiushan Yin, Wei-Hua Chen, Juan Du, Vicent Pelechano Liu et al. present s5PSeq, a rapid 4-h sequencing workflow that detects antibiotic-induced ribosome stalling within minutes to provide a molecular readout of phenotypic antimicrobial susceptibility. Its compatibility with nanopore sequencing enables fast and affordable phenotypic AMR testing, including in complex mixed-species samples. MASTR-seq enables multiplexed analysis of short tandem repeats with sequencing Chuanbin Su, Han-Seul Ryu, Keerthivasan Raanin Chandradoss, Thomas Malachowski, Ravi Boya, Linda Zhou, Hoa Emma Nguyen, Esteban O. Mazzoni, Kristen J. Brennand, Jennifer E. Phillips-Cremins Su et al. present MASTR-seq, a cost-effective, high-throughput method for precisely measuring short tandem repeat tract length and DNA methylation at a pre-defined locus at single-molecule resolution using nanopore sequencing. Comprehensive cellular analysis with single-nucleus RNA-seq of archived PAXgene whole blood samples Ojasvi Chaudhary, Mia Steinberg, Grant Duclos, Peter Gathungu, Manisha Rao, Rogelio Aguilar, Varsha Shankarappa, Chris Rands, Xi Chen, Rebecca A. Halpin, Elizabeth Galery, Joseph Boland, Maurizio Scaltriti, Brian Dougherty, Asaf Rotem Chaudhary et al. introduce a single-cell-based method for gene expression of preserved PAXgene blood samples, allowing for simplified collection/processing and providing broader immune profiling by the inclusion of granulocytes. This methodology will help enable large-scale research with clinical samples. Interpretable learning of temporal cellular dynamics from single-cell data Idris Kouadri Boudjelthia, Salvatore Milite, Nour El Kazwini, Yuanhua Huang, Andrea Sottoriva, Guido Sanguinetti Kouadri et al. introduce NeuroVelo, a physics-informed neural ODE model that infers cell-state trajectories and interpretable gene regulatory mechanisms from static scRNA-seq. Across five datasets, NeuroVelo matches or outperforms RNA velocity baselines and recovers ChIP-seq-supported regulatory networks. Ontology-aware DNA methylation classification with a curated atlas of human tissues and cell types Mirae Kim, Ruth Dannenfelser, Yufei Cui, Genevera Allen, Vicky Yao Kim et al. assemble a large atlas of healthy human DNA methylation and introduce an ontology-aware model that learns hierarchical tissue identity. By identifying a compact CpG signature of normal tissue identity, the work offers a reference baseline that could complement methylation aging clocks in future biological and clinical applications. Scalable nonparametric clustering with unified marker gene selection for single-cell RNA-seq data Chibuikem Nwizu, Madeline Hughes, Michelle L. Ramseier, Andrew W. Navia, Alex K. Shalek, Nicolo Fusi, Srivatsan Raghavan, Peter S. Winter, Ava P. Amini, Lorin Crawford Nwizu et al. develop a nonparametric statistical model that simultaneously clusters single-cell data and identifies cell type marker genes. They demonstrate the utility of their approach on simulations and five different publicly available single-cell RNA sequencing (scRNA-seq) studies. Application of spectral flow cytometry for comprehensive detection of immune metabolism in patient-derived microsamples Yang Bai, Yuqing Wang, Yicheng Fu, Zhengyang Guo, Zhaoyuan Liang, Liu Yang, Jiawei Ribaudo, Dan Liu, Yanfang Li, Ting Zhang, Lixiang Xue, Jianling Yang, Huilin Liu, Xianlong Li, Jie Zhang Bai et al. develop a spectral flow cytometry platform for high-dimensional analysis of single-cell immunometabolic signatures using small amounts of peripheral blood. Application to samples from patients with heart failure suggests a metabolic shift toward glucose use in T cell subsets, demonstrating the method’s potential for precision studies of immunometabolism in disease. Tissue morphology predicts telomere shortening in human tissues Anamika Yadav, Kyle Alvarez, Akanimoh Adeleye, Yu Xin Wang, Michael Jackson, Sanju Sinha Yadav et al. present TLPath, a deep learning framework tool that predicts telomere length from routine histopathology images. This approach reveals that physical changes in tissue are associated with telomere shortening. TLPath can enable large-scale telomere biology studies using existing tissue archives. Resource Comparative analysis of nuclei isolation methods for brain single-nucleus RNA sequencing Holly N. Kersey, Dominic J. Acri, Luke C. Dabin, Kelly A. Hartigan, Richard Mustaklem, Jung Hyun Park, Jungsu Kim Kersey et al. systematically evaluate three nuclei isolation methods for brain snRNA-seq, demonstrating that protocol choice markedly affects data quality metrics, including nuclei yield and ambient RNA contamination levels, as well as cell type proportions. Notably, a machine-assisted approach minimizes technical variability, providing consistent transcriptional signatures across glial and neuronal populations. View the entire Table of Contents online