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

W. De Lau, P. Kujala, K. Schneeberger, S. Middendorp, V.S. Li, N. Barker, A. Martens, F. Hofhuis, R.P. DeKoter, P.J. Peters, E. Nieuwenhuis, H. Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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-called M cells. 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 that M cells 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 in M cells. In SpiB(-/-) mice, M cells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can induce M cell development in vivo. We show that in intestinal organoid ("minigut") cultures, stimulation with RankL induces SpiB expression within 24 h and expression of other M cell markers subsequently. We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells.
Original languageEnglish
Pages (from-to)3639-3647
JournalMolecular and Cellular Biology
Volume32
Issue number18
DOIs
Publication statusPublished - 2012

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