Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration.
Hirohito AboBenoit ChassaingAkihito HarusatoMiguel QuirosJennifer C BrazilVu L NgoEmilie ViennoisDidier MerlinAndrew T GewirtzAsma NusratTimothy L DenningPublished in: Nature communications (2020)
Gut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5+ stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5+ stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5+ intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.
Keyphrases
- stem cells
- early life
- gene expression
- radiation induced
- cell proliferation
- oxidative stress
- induced apoptosis
- high fat diet induced
- type diabetes
- cell therapy
- high glucose
- signaling pathway
- dna methylation
- ms ms
- radiation therapy
- insulin resistance
- mental health
- single cell
- bone marrow
- adipose tissue
- mechanical ventilation
- acute respiratory distress syndrome
- cell cycle
- wild type
- drug induced
- extracorporeal membrane oxygenation