Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium | Zendy

Ellen N. Elliott | Zendy; Karyn L. Sheaffer | Zendy; Jonathan Schug | Zendy; Thaddeus S. Stappenbeck | Zendy; Klaus H. Kaestner | Zendy

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Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium

Author(s) -

Ellen N. Elliott,

Karyn L. Sheaffer,

Jonathan Schug,

Thaddeus S. Stappenbeck,

Klaus H. Kaestner

Publication year - 2015

Publication title -

development

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.15

H-Index - 36

eISSN - 1477-9129

pISSN - 0950-1991

DOI - 10.1242/dev.117341

Subject(s) - biology , dnmt1 , dna methylation , dna methyltransferase , microbiology and biotechnology , organoid , progenitor cell , stem cell , genetics , gene expression , gene

The DNA methyltransferase Dnmt1 maintains DNA methylation patterns and genomic stability in several in vitro cell systems. Ablation of Dnmt1 in mouse embryos causes death at the post-gastrulation stage; however, the functions of Dnmt1 and DNA methylation in organogenesis remain unclear. Here, we report that Dnmt1 is crucial during perinatal intestinal development. Loss of Dnmt1 in intervillus progenitor cells causes global hypomethylation, DNA damage, premature differentiation, apoptosis and, consequently, loss of nascent villi. We further confirm the crucial role of Dnmt1 during crypt development using the in vitro organoid culture system, and illustrate a clear differential requirement for Dnmt1 in immature versus mature organoids. These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts.

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