Single-cell and spatial maps reveal divergent epigenomic paths in human reprogramming
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A bioRxiv preprint posted on 2026-10-22 maps epigenomic heterogeneity and spatial organization during human fibroblast reprogramming. Researchers combined paired single-nucleus multiomics with spatial transcriptomics across reprogramming time courses from four individuals. They found that transcriptional and epigenomic changes are not synchronized along successful and failed trajectories: DNA methylation heterogeneity declines during successful reprogramming, while failed populations either retain fibroblast-like methylation or fail to fully establish the iPSC regulatory state after chromatin opening and demethylation. Spatial analysis shows successful and failed populations adopt distinct spatial organization before overt iPSC colonies form, with successful reprogramming hotspots visible by day 3. The work is a preprint and has not yet undergone peer review.
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- bioRxivPickEpigenomic heterogeneity and spatial organization during human reprogramming
Researchers integrated paired single-nucleus multiomics and spatial transcriptomics across human fibroblast reprogramming time courses from four individuals, finding that transcriptional and epigenomic changes are not synchronized along successful and failed trajectories. DNA methylation heterogeneity declines during successful reprogramming, while failed populations either retain fibroblast-like methylation or fail to fully establish the iPSC regulatory state after chromatin opening and demethylation. Spatial analysis shows the two populations organize differently before overt iPSC colonies form, with successful reprogramming hotspots visible by day 3.
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