Spatial constraint and transient reversion initiate intestinal regeneration

Abstract:: The cellular origins of intestinal stem cell regeneration in the crypt base after localised damage is uncertain due to an incomplete quantitative understanding of the interplay of the cell behaviours that maintain and restore intestinal crypts. Here, machine learning processing of combined lineage tracing and comprehensive profiling of single cell transcriptional data assigns crypt position and cell cycle status to each intestinal crypt cell. This allows population dynamics models to be applied to provide quantitative insights into short- and long-term cellular behaviours in homeostasis and after intestinal stem cell ablation. This reveals that passive retrograde movement previously implicated in the homeostatic maintenance of the intestinal stem cell pool is not sufficient for its restoration after ablation. Rather, 10% of the regenerated stem cell pool is seeded from a localised suprabasal cell population marked by acquisition of foetal gene expression, including Ly6a, with 90% of stem cells being restored subsequently by expansion of this subpopulation.

Authors:: D Winton, D Khamis, A Demian, E Moutin, G Giavara, M Colombé, S Kozar, R Kemp, M Morgan, E Morrissey

Themes