Peyer's patch M cells derived from Lgr5+ stem cells require SpiB and are induced by RankL in cultured miniguts

Wim de Lau, Pekka Kujala, Kerstin Schneeberger, Sabine Middendorp, Vivian S.W. Li, Nick Barker, Anton Martens, Frans Hofhuis, Rodney P. DeKoter, Peter J. Peters, Edward Nieuwenhuis, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

184 Citaten (Scopus)

Samenvatting

Peyer's patches consist of domains of specialized intestinal epithelium overlying gut-associated lymphoid tissue (GALT). Luminal antigens reach the GALT by translocation through epithelial gatekeeper cells, the so-calledMcells. We recently demonstrated that all epithelial cells required for the digestive functions of the intestine are generated from Lgr5-expressing stem cells. Here, we show thatMcells also derive from these crypt-based Lgr5 stem cells. The Ets family transcription factor SpiB, known to control effector functions of bone marrow-derived immune cells, is specifically expressed inMcells. In SpiB-/-mice, Mcells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can induceMcell development in vivo. We show that in intestinal organoid (" minigut" ) cultures, stimulation with RankL induces SpiB expression within 24 h and expression of otherMcell markers subsequently. We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop intoMcells.

Originele taal-2Engels
Pagina's (van-tot)3639-3647
Aantal pagina's9
TijdschriftMolecular and Cellular Biology
Volume32
Nummer van het tijdschrift18
DOI's
StatusGepubliceerd - sep. 2012
Extern gepubliceerdJa

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