Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development

Author:

Ichinose Mari12,Suzuki Nobumi123,Wang Tongtong12,Wright Josephine A.12,Lannagan Tamsin R. M.12,Vrbanac Laura12,Kobayashi Hiroki12,Gieniec Krystyna A.12,Ng Jia Q.12,Hayakawa Yoku3ORCID,García-Gallastegui Patricia4,Monsalve Eva M.5,Bauer Steven R.6,Laborda Jorge5,García-Ramírez J. J.5,Ibarretxe Gaskon4,Worthley Daniel L.2,Woods Susan L.12ORCID

Affiliation:

1. School of Medicine, The University of Adelaide, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia

2. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

3. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

4. Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country, Bizkaia, Spain

5. Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain

6. Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland

Abstract

Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.

Funder

Kanzawa Medical Research Foundation

Cancer Council SA Beat Cancer Project

Greaton International

Kakenhi grant in aid for scientific research

Astellas Foundation for Research on Metabolic Disorders

Department of Health, Australian Government | National Health and Medical Research Council

MEXT | Japan Society for the Promotion of Science

Takeda Science Foundation

Uehara Memorial Foundation

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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