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Id2 controls specification of Lgr5 + intestinal stem cell progenitors during gut development
Author(s) -
Nigmatullina Lira,
Norkin Maxim,
Dzama Margarita M,
Messner Berith,
Sayols Sergi,
Soshnikova Natalia
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694959
Subject(s) - biology , stem cell , progenitor cell , lgr5 , microbiology and biotechnology , cancer stem cell
Abstract The adult intestinal stem cells ( ISC s), their hierarchies, mechanisms of maintenance and differentiation have been extensively studied. However, when and how ISC s are established during embryogenesis remains unknown. We show here that the transcription regulator Id2 controls the specification of embryonic Lgr5 + progenitors in the developing murine small intestine. Cell fate mapping analysis revealed that Lgr5 + progenitors emerge at E13.5 in wild‐type embryos and differ from the rest on the intestinal epithelium by a characteristic ISC signature. In the absence of Id2, the intestinal epithelium differentiates into Lgr5 + cells already at E9.5. Furthermore, the size of the Lgr5 + cell pool is significantly increased. We show that Id2 restricts the activity of the Wnt signalling pathway at early stages and prevents precocious differentiation of the embryonic intestinal epithelium. Id2‐deficient embryonic epithelial cells cultured ex vivo strongly activate Wnt target genes as well as markers of neoplastic transformation and form fast growing undifferentiated spheroids. Furthermore, adult ISC s from Id2‐deficient mice display a distinct transcriptional signature, supporting an essential role for Id2 in the correct specification of ISC s.