A spatial and temporal transcriptomic atlas of mouse intestinal regeneration in the jejunum
TL;DR
The authors use spatial transcriptomics to map the mouse intestine over time after radiation injury, revealing shifts in villus zonation, spatially restricted interferon signaling, altered stem cell populations and a surge in gene transcription that may help fuel recovery.
Abstract
The intestinal epithelium exhibits a remarkable capacity for regeneration following injury, yet the spatial and temporal dynamics of the damage-repair cycle remain incompletely understood. We present a spatial transcriptomics atlas of ionizing radiation-induced injury and repair in the mouse jejunum, capturing mRNA from 16,921 genes across approximately 26 million bins at 2-µm resolution in 23 biological samples spanning six days post-irradiation. Analysis reveals transcriptional patterns and niche signals undetectable by bulk or single-cell approaches, including spatially restricted interferon-target gene activation, an altered differentiation trajectory in the lower villus during early repair, two transcriptionally distinct crypt regenerative cell populations, and global transcriptional upregulation consistent with hypertranscription as a hallmark of intestinal regeneration, with evidence for hypertranscription extending to human Crohn’s disease. In this work, we provide a spatiotemporal atlas of mouse intestinal regeneration at subcellular 2-µm resolution that will inform future therapeutic strategies for inflammatory bowel diseases and gastrointestinal pathologies arising from injury or cancer therapy. The intestinal epithelium efficiently regenerates after injury, yet the dynamics underlying this process are not fully understood. Here, the authors use spatial transcriptomics to map the mouse intestine over time after radiation injury, revealing shifts in villus zonation, spatially restricted interferon signaling, altered stem cell populations and a surge in gene transcription that may help fuel recovery.