Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration.,Nature Communications

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Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-24 , DOI: 10.1038/s41467-019-14258-z
Hirohito Abo ₁ , Benoit Chassaing _{1,

2,

3,

4} , Akihito Harusato ₁ , Miguel Quiros ₅ , Jennifer C Brazil ₅ , Vu L Ngo ₁ , Emilie Viennois ₆ , Didier Merlin _{6,

7} , Andrew T Gewirtz ₁ , Asma Nusrat ₅ , Timothy L Denning ₁

Affiliation

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.

中文翻译：

微生物群在生命早期诱导的类红细胞分化调节因子-1促进肠道干细胞的增殖和再生。

肠道菌群及其代谢产物在调节肠道稳态中起着重要作用。然而，生命早期微生物群对肠道发育的影响尚不完全清楚。在这里，我们证明了断奶（exGF）的无病菌（GF）小鼠与无特定病原体（SPF）小鼠的共居导致肠道基因表达的改变。我们的研究结果表明，在SPF发育过程中诱导了一个高度差异表达的基因，红系分化调节因子1（Erdr1），但GF或exGF小鼠却没有，并且定位于Lgr5 +干细胞和转运扩增（TA）细胞。Erdr1的功能是在上皮细胞中诱导Wnt信号传导，增加Lgr5 +干细胞的扩增并促进肠道类器官的生长。此外，Erdr1加速了体外的刮伤闭合，在体内辐射诱导的损伤后增加Lgr5 +肠干细胞的再生，并增强从葡聚糖硫酸钠（DSS）诱导的结肠损伤的恢复。总的来说，我们的研究结果表明，生命早期的微生物群可控制Erdr1介导的肠上皮增殖和再生，以应对粘膜损伤。

更新日期：2020-01-24

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