Developmental factors drive the compartmentalized and discontinuous maturation of the small intestinal epithelium during the early postnatal period.

Authors

Johannes Schöneich, Aline Dupont, Stefan Schlößer, Mingbo Cheng, Matthias A Schmitz, Isabel Richter, Narasimha Murthy Keshava Prasad Gubbi, Kaiyi Zhang, Tiago Maié, Asmae Laouina, Sofia Jäverfelt, Fabian Imdahl, Christophe Toussaint, Antoine-Emmanuel Saliba, Christoph Kuppe, Oliver Pabst, Thaher Pelaseyed, Ivan G Costa, Mathias W Hornef

Published in

PLoS biology. Volume 24. Issue 8. Pages e3003212. Aug 03, 2026. Epub Aug 03, 2026.

Abstract

The temporal, spatial, and cellular diversity of the small intestinal epithelium during the postnatal period, a critical time window that accompanies the transition from placental energy supply to enteral feeding, and the establishment of the enteric microbiota and postnatal immune maturation, has not been systematically investigated. Here, we used laser capture microdissection and bulk RNA-Seq, proteomics, and single cell RNA-Seq to analyze the total, organ site, crypt- and villus-specific intestinal epithelium of specific pathogen-free, germ-free, and Salmonella-infected mice during the postnatal period. We identified key temporal and organ-site specific expression patterns that revealed a weak effect of the microbiota but strong influence of developmental regulators during early life. We also determined age-dependent signaling pathway and transcription factor activity and characterized age- and cell type-specific developmental trajectories revealing a distinct compartmentalized maturation process along the proximal-to-distal length and crypt-villus axis and a discontinuous appearance of goblet/Paneth cell and absorptive enterocyte transcriptional profiles. Finally, we described the cell type-specific response to neonatal enteric infection. Taken together, our findings identify the epithelium as an integral element in the maturation of postnatal mucosal tissues and in the establishment of host-microbe homeostasis.

PMID:
42546040
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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