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

PLoS Biology, vol. 24, pp. e3003212

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.

Authors 19

1. Johannes Schöneich Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

2. Aline Dupont Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

3. Stefan Schlößer Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

4. Mingbo Cheng Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

5. Matthias A. Schmitz Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

6. Isabel Richter Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

7. Narasimha Murthy Keshava Prasad Gubbi Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

8. Kaiyi Zhang Aachen Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany

9. Tiago Maié Aachen Institute for Computational Genomics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

10. Asmae Laouina Aachen Institute for Molecular Medicine

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Molecular Medicine, RWTH Aachen University Hospital, Aachen, Germany

11. Sofia Jäverfelt

    University of Gothenburg

    Affiliation as printed

    Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

12. Fabian Imdahl

    Helmholtz Institute for RNA-based Infection Research

    Affiliation as printed

    Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany

13. Christophe Toussaint

    University of Würzburg · Helmholtz Institute for RNA-based Infection Research

    Affiliation as printed

    Cluster for Nucleic Acid Sciences and Technologies - NUCLEATE, Würzburg, Germany

    Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany

    Institute of Molecular Infection Biology Faculty of Medicine, University of Würzburg, Würzburg, Germany

14. Antoine‐Emmanuel Saliba

    University of Würzburg · Helmholtz Institute for RNA-based Infection Research

    Affiliation as printed

    Cluster for Nucleic Acid Sciences and Technologies - NUCLEATE, Würzburg, Germany

    Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany

    Institute of Molecular Infection Biology Faculty of Medicine, University of Würzburg, Würzburg, Germany

15. Christoph Kuppe Aachen Center of Excellence in Nephrology Department of Nephrology and Hypertension Rheumatology and Immunology (Medical Clinic II) Medical Faculty

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Center of Excellence in Nephrology, University Hospitals Aachen Cologne Dusseldorf, Aachen, Germany

    Department of Nephrology and Hypertension, Rheumatology and Immunology (Medical Clinic II), Medical Faculty RWTH Aachen, Aachen, Germany

16. Oliver Pabst Aachen Institute for Molecular Medicine

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Molecular Medicine, RWTH Aachen University Hospital, Aachen, Germany

17. Thaher Pelaseyed

    University of Gothenburg

    Affiliation as printed

    Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

18. Ivan G. Costa Aachen Institute for Computational Genomics

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany

19. Mathias Walter Hornef corresponding Aachen Institute of Medical Microbiology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany