Single Cell News

A full-length single nuclei transcriptomic atlas of human skeletal muscle insulin resistance

Katie Whytock ... Bret Goodpaster integrated full-length single-nucleus transcriptomics with gold-standard stable isotope-labeled hyperinsulinemic-euglycemic clamps to generate a nucleus-resolved transcriptomic atlas of skeletal muscle insulin resistance.

Key points
✨Previously unrecognized myonuclear populations whose proportions associate with insulin sensitivity, revealing MYH7B+ myonuclei are metabolically favorable over EGF+ myonuclei
✨Highly nucleus-specific molecular programs obscured when using surrogate fasting indices
✨Zinc transporter ZIP14 as a positive regulator of insulin-stimulated glucose uptake
✨EGF signaling implicated in impaired branched-chain amino acid catabolism and inflammatory cross-talk within the skeletal muscle niche.

#singlecellnews

MAP: a knowledge-driven framework for predicting single-cell responses for unprofiled drugs

Jinghao Feng ... Weidi Xie presented MAP, a framework that integrates structured biological knowledge into cellular perturbation modeling and supports zero-shot prediction for small molecules with scarce or absent perturbation profiles.

Key points
🔸 MAP-KG, a large-scale knowledge graph tailored for cellular perturbation modeling that unifies 14 public resources, spanning 187k drugs, 23k genes, and 694k mechanistic relationships
🔸 A knowledge-driven pre-training strategy that aligns molecular structures, protein sequence features, and textual mechanistic descriptions into a unified embedding space
🔸 Evaluation of MAP under two zero-shot generalization regimes: unseen cell type-drug combinations and the stricter setting of unprofiled drugs
🔸 Pathway-level functional analysis via GSEA for in-silico screening, where MAP predicts coherent, mechanism-consistent programs on unprofiled candidate drugs.

#singlecellnews

Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging

Ziyu Lu ... Junyue Cao constructed a single-cell chromatin accessibility atlas spanning 21 mouse tissues across three age groups and both sexes to investigate organism-wide cellular alterations and epigenomic dynamics during aging.

Key points
📍One-quarter of 536 organ-specific cell types and 1828 finer-grained subtypes exhibit considerable age-related population shifts
📍Cellular states from broadly distributed lineages display synchronized dynamics with age, indicating systemic signals that coordinate these changes
📍Identification of both intrinsic regulators (chromatin peaks, transcription factor activity) and extrinsic factors (cytokine programs) underlying these shifts
📍~40% of aging-associated population dynamics are sex-dependent, with tens of thousands of peaks altered exclusively in one sex

#singlecellnews

Whole-organ and whole-body 3D atlases enable cellome-wide profiling

Shota Yoshida ... Hiroki Ueda presented the CUBIC Organ/Body Atlas, a set of three-dimensional single-cell-resolution references for eleven adult mouse organs and a neonatal whole-mouse body. 

Key points
📌Optimized tissue clearing protocols
📌An imaging system achieving sufficient working distance and axial resolution for organ-/body-wide three-dimensional imaging and subsequent cell nuclei detection
📌Comparative analysis among multiple samples at single-cell resolution
📌Applications in organ development studies, disease state analysis, and whole-body immune cell profiling with three-dimensional immunostaining.

#singlecellnews

Volumetric DNA microscopy for mapping spatial transcriptomes in three dimensions

Nianchao Qian ... Joshua Weinstein developed volumetric DNA microscopy, a scalable, optics-free approach for spatial transcriptome profiling directly within intact biological specimens.

Key points
✔️The complete workflow including in situ cDNA synthesis, spatial encoding through DNA nanoball formation, dual-scale proximity bridging between neighboring nanoballs and spatial reconstruction via geodesic spectral embedding
✔️Anchored rolling-circle amplification capturing short-range (~1 µm) proximities essential for high resolution
✔️A hydrogel-based in vitro transcription (IVT) integrating longer-range interactions necessary for connecting distant regions and reconstructing global morphology
✔️Generation of sequencing libraries within 7–8 days
✔️Template-free 3D reconstructions of whole organisms or tissues at 1–2 µm median resolution.

#singlecellnews

Single-cell and spatial methods for multimodal functional glycan profiling in tissues

Ankit Basak ... Laura Kiessling presented two platforms, single-cell outlining and transcriptome sequencing (scGOATseq) and GlycoScope, which use human lectins to enable functional glycan accessibility into single-cell and spatial multiomic measurements.

Key points
⚡️Quantifying lectin-accessible glycan states with gene expression
⚡️Multiplexed in situ co-detection of glycans and proteins in tissues
⚡️Identification of stimulus-specific glycan remodeling in immune cells and distinct Siglec-ligand-defined programs not captured by traditional methods.

#singlecellnews