A cellular cross-species RNA-seq atlas captures the trannoscriptional dynamics of myogenesis

Fernando Valdivieso-Rivera ... Alexander Bartelt presented a high-quality RNA-sequencing dataset profiling trannoscriptional dynamics in both mouse (C2C12) and human (LHCN-M2) myogenic cells.

Key points
📌The major trannoscriptional shifts occurring in myoblasts, marking the onset of differentiation
📌Shared global features of myogenesis but also distinct regulatory trajectories
📌Early upregulation of human differentiation followed by suppression of metabolic and stress-related pathways
📌Persistent elevation of structural and ECM-associated programs in human differentiation
📌Early inflammatory activation and later enrichment of metabolic and contractile pathways typical of mature myotubes in mouse C2C12 cells
📌Decreasing cross-species correlation over time, indicating progressive reinforcement of species-specific differentiation programs.

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Dendritic cell subsets and states unraveled across human juxtatumoral and malignant tissues

Kevin Mulder … Charles-Antoine Dutertre integrated dendritic cells (DCs) from 13 tumor tissues across 40 datasets to create a pDC + mDC-VERSE (DC-VERSE) and an mDC-VERSE single-cell RNA-sequencing compendium.

Key points
🔹Identifying a CD207+CD1a+ DCs inside the most tumors
🔹CD207+ DCs inversely correlate with T cell clonal expansion and CD8+ resident memory T cells
🔹CD207+ DCs are predominantly embedded within tumor nests, while all the other DCs are mainly detected within the tumor stroma
🔹CD207+ DCs are associated with poor survival following immune checkpoint blockade, in contrast to DC1s and CCR7+ mDCs
🔹CD207+ DCs show an impaired capacity to produce key cytokines

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RamanOmics decodes spatial vibrational-molecular architecture and rewiring in aging and repair

Ke Zhang ... Jian Shu presented RamanOmics, a multimodal framework that integrates snRNA-seq, spatial trannoscriptomics, and label-free Raman imaging to map the spatial vibrational-biochemical and molecular architecture of aging and senescence directly in intact tissues.

Key points
🔸A machine learning derived multimodal barcode that quantitatively integrates biochemical and trannoscriptional features
🔸A conserved branched-chain fatty-acid-linked biochemical profile and Raman signature (1131-1135 cm-1) that robustly marks p21+ senescent cells
🔸Lung senescent cells enriched for extracellular matrix remodeling and TGF-b signaling
🔸Skin senescence dominated by keratinization and barrier homeostasis modules
🔸Coordinated reactivation of barrier-repair programs in senescent cells, confirming biological generalizability beyond steady-state aging

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Novae: a graph-based foundation model for spatial trannoscriptomics data

Quentin Blampey ... Paul-Henry Cournède designed Novae, a graph-based foundation model that extracts representations of cells within their spatial contexts.

Key points
✔️Training on a large dataset of nearly 30 million cells across 18 tissues
✔️Zero-shot domain inference across multiple gene panels, tissues and technologies
✔️Сorrection of batch effects and constructing a nested hierarchy of spatial domains
✔️Various downstream tasks, including spatially variable gene or pathway analysis and spatial domain trajectory analysis
✔️Available here

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RoCK and ROI: single-cell trannoscriptomics with multiplexed enrichment of selected trannoscripts and region-specific sequencing

Giulia Moro ... Konrad Basler presented RoCK and ROI, a simple and highly versatile scRNA-seq-based method designed to capture specific trannoscripts and to selectively sequence regions of interest.

Key points
📍Targeted capture to enrich for key trannoscripts
📍The detection and identification of cell types and complex phenotypes
📍Directing a subset of reads to a specific region of interest via selective priming
📍Retrieval of specific sequence information without compromising overall single cell trannoscriptome information
📍Validation across diverse biological systems.

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Connecting spatial regions to clinical phenotypes by transferring knowledge from bulk patient data

Amgalan Bayarbaatar ... Teresa Maria Przytycka developed SpacePhenotyper, a method to overcome the challenges of predicting clinical phenotypes for spatial regions.

Key points
📌Algebraic spectral techniques to transfer the predictive relationship between gene expression and clinical phenotypes from bulk gene expression to spatially resolved trannoscriptomics
📌Capture of a gene expression pattern that is predictive of the phenotype of interest in the form of a vector, the Eigen-Patient, which is then used to quantify the phenotype in spatial spots
📌Studying influence of spatial heterogeneity of breast cancer on residual cancer burden after treatment.

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DISCO-seq: 3D single-cell trannoscriptomics of intact biological systems

Harsharan S. Bhatia, ... Ali Ertürk developed DISCO-seq, a tissue-clearing chemistry that enables superior RNA accessibility providing a robust framework for unbiased spatial trannoscriptomics in intact specimens.

Key points
📍 Integration of whole-organ or organism 3D imaging with both untargeted and targeted trannoscriptomics
📍 Versatility across multiple biological systems and trannoscriptomic platforms
📍 Validation of performance in the mouse brain and mapping of SARS-CoV-2 S1 protein deposition
📍 A physical framework for mapping cells and their molecular states within their native structural and functional contexts

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Artificial intelligence revolution in trannoscriptomics: from single cells to spatial atlases

Shixin Li ... Chao Zhang surveyed AI applications across the trannoscriptomic analysis workflow – from initial preprocessing through key downstream analyses such as trajectory inference, gene regulatory network reconstruction, and spatial domain detection.

Key points
🔸The developmental trajectory and evolving trends of AI models
🔸Advantages, limitations, and domain-specific applicability of AI models
🔸Key innovations, ongoing challenges, and future directions
🔸Practical guidance to assist in model selection and support in the design of novel AI tools
🔸An online companion supplement providing an in-depth look at all methods: https://zhanglab-kiz.github.io/review-ai-trannoscriptomics

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A single-cell cytokine dictionary of human peripheral blood

Lukas Oesinghaus ... Fabian Theis presented a Human Cytokine Dictionary, the largest single-cell perturbation dataset of primary human immune cells to date.

Key points
✨9,697,974 human PBMC from 12 donors stimulated in vitro with 90 different cytokines
✨Donor-specific response variation and robust consensus cytokine signatures across individuals
✨Cytokine-induced immune programs that organize responsive genes into data-driven, biologically interpretable functional modules
✨Higher-order cell-to-cell and cytokine-to-cytokine communication networks exemplified by an IL-32-β-initiated signaling cascade
✨The interpretation of cytokine-driven immune responses in other studies and disease contexts, including systemic lupus erythematosus, multiple sclerosis, and non-small cell lung carcinoma.

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Single-cell trannoscriptomics reveals a conserved embryonic progenitor in different human cancers

Anna Khozyainova, Vera Subrakova … Evgeny Denisov integrated scRNA-seq data from three distinct cancers (lung adenocarcinoma, melanoma, and medulloblastoma) and embryoid bodies to reveal the molecular parallels between oncogenesis and early human development. 

Key points 
🔹An embryonic progenitor cell population shared across ontogenetically distinct cancers
🔹The E2F-TFDP regulatory activity and the 25-gene signature defining this population
🔹Root position of the progenitor population in differentiation trajectories across distinct cancers
🔹Spatial enrichment of the 25-gene signature in tumor regions and preneoplastic lesions of the bronchial epithelium.

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Cell-type-specific regulomes critical for immune- and aging-related diseases

Yunlong Ma ... Jianzhong Su presented scMORE, a method that integrates single-cell trannoscriptomes and chromatin accessibility with GWAS summary statistics to identify cell-type-specific eRegulons associated with diseases.

Key points
✅ Capturing trait-relevant cellular features
✅ Robust performance across simulated and real single-cell datasets, and GWASs for 31 immune- and aging-related traits, including Parkinson’s disease (PD)
✅ 77 aging-relevant eRegulons implicated in PD across seven brain cell types
✅ Sex-dependent dysregulation of the eRegulons in PD neurons compared to both young and aged groups.

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An integrated view of the structure and function of the human 4D nucleome

Job Dekker … Feng Yue described efforts by the 4D Nucleome Project to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts.

Key points
✔️Extensive catalogues of more than 140,000 looping interactions per cell type
✔️Detailed classifications and annotations of chromosomal domain types and their subnuclear positions
✔️Single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements
✔️The unique strengths of different genomic assays for studying the 4D nucleome
✔️Connections between chromosome folding, nuclear organization, chromatin looping, gene trannoscription and DNA replication
✔️Computational methods to predict genome folding from DNA sequence and to discover genetic variants affecting genome structure and function.

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Spatiotemporal cellular map of the developing human reproductive tract

Valentina Lorenzi … Roser Vento-Tormo generated a highly resolved, spatiotemporal, multi-omic map of the entire human reproductive tract (excluding the gonads) in the first and second trimesters.

Key points
📌52 reproductive-tract-specific cell types in 89 human samples spanning 6-21 post-conceptional weeks
📌Potential regulators, previously unknown genes, and signalling events involved in sexual dimorphism in reproductive organs
📌Establishment patterns of the HOX code in distinct reproductive organs
📌Epithelial regionalization of the fallopian tube and epididymis, which probably contribute to sperm maturation and capacitation, during development
📌Vulnerability of the fetal uterine epithelium to oestrogen-mimicking endocrine disruptors.

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SpaceBar enables single-cell-resolution clone tracing with imaging-based spatial trannoscriptomics

Grant Kinsler ... Yael Heyman reported SpaceBar, which enables simultaneous clone tracing and spatial gene expression profiling with standard imaging-based spatial trannoscriptomics pipelines.

Key points
📍A library of 96 synthetic barcode sequences that combinatorially labels each cell
📍The barcodes can be detected with standard single-molecule RNA FISH-based methods, such as MERFISH and seqFISH
📍The barcodes are also compatible with Xenium (10x Genomics) and CosMx SMI (NanoString)
📍Best suited for identifying longer-lived expression memory
📍Limitation: high transduction efficiencies are needed to achieve high diversity of labeled clones.

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A high-resolution atlas of the brain predicts lineage and birth order underlying neuronal identity

Aaron Allen ... Stephen Goodwin generated the first high-resolution, single-cell trannoscriptomic atlas of the adult Drosophila melanogaster central brain by integrating multiple datasets, achieving an unprecedented 10-fold coverage of every neuron in this complex tissue. 

Highlights
⚡️Single-cell atlas reveals 4,167 neuronal subtypes in adult Drosophila brain
⚡️Lineage and birth order shape adult neuron trannoscriptomic identities
⚡️Distinct trannoscription factor families act along spatial and temporal axes of neuron specification
⚡️Intersectional genetic tools bridge gene expression to anatomy and circuit function.

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Scoring gene importance by interpreting single-cell foundation models

Maxwell Gold ... Tommaso Biancalani introduced SIGnature, a framework for scoring gene importance by leveraging attributions derived from single-cell RNA-sequencing foundation models.

Key points
🔸Reducing technical noise, emphasizing regulatory genes, and facilitating cross-dataset comparison — a core challenge for scRNA-seq
🔸SIGnature utility using the MS1 monocyte signature, a poorly understood gene program activated in severe COVID-19 and sepsis
🔸Revealing and experimental validation of novel associations between the MS1 signature and multiple hyperinflammatory conditions, including Kawasaki disease.

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Decoding cnidarian cell type gene regulation

Anamaria Elek ... Arnau Sebé-Pedrós profiled chromatin accessibility in 60,000 cells from whole adults and gastrula-stage embryos of the sea anemone Nematostella vectensis.

Key points
✔️112,728 putative CREs and their activity across cell types
✔️Pervasive combinatorial enhancer usage and distinct promoter architectures
✔️Inferring cell type similarities that reflect known ontogenetic relationships
✔️Reconstruction of the GRNs that define cnidarian cell types
✔️The regulatory complexity underlying cell differentiation
✔️Conserved principles in animal gene regulation.

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A new class of proteinaceous biomaterial with unprecedented properties in unicellular eukaryotes

Maximilian Ganser ... Sabine Agatha identified the main component of the proteinaceous shells by combining single-cell trannoscriptomic analyses and mass-spectrometry of the shells from the tintinnid Schmidingerella.

Key points
✅ The shells of tintinnid ciliates, a group of planktonic unicellular eukaryotes, are composed of self-assembling structural proteins
✅ The shells form in water, are structurally diverse, and show exceptional resistance against high temperatures and the strongest chemicals
✅ The shell-forming proteins are exceptionally rich in aromatic residues and possess a unique architecture with flexible, unfolded segments connecting highly stable beta-sheets
✅ This easily accessible system promises new aspects to advance current biomaterial design.

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An interpretable multi-instance learner decodes cellular recruitment from spatially resolved trannoscriptomics

Jia Yao ... Tao Wang introduced an algorithm called Spatial Analysis of Cellular Engagement and Recruitment (spacer), a fully interpretable multi-instance deep learner designed to decrypt the “spatial language” of tissues.

Key points
📍Studying how stromal and immune cells are recruited into tumors and heart during myocarditis
📍Novel biological insights not affordable by prior spatial data analysis tools
📍Genes encoding more immunogenic peptides and involved in developmental pathways are more potent in recruiting T cells to local tumor sites
📍The recruitment of B cells and macrophages is stipulated by a different molecular program
📍Expression of mucins in tumor cells repels T cell localization
📍Uncovering T cell-intrinsic features that determine their localization
📍CD4+ T cells are more responsive than CD8+ T cells in the heart during myocarditis

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Dear friends!

ASCA wishes you a Merry Christmas and a Happy New Year🎄☃️

May 2026 brings interesting and successful single-cell experiments with less batch effect, superior data integration, and reliable cell type annotation! 🥂