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Peyer's patch M cells derived from Lgr5+ stem cells require SpiB and are induced by RankL in cultured miniguts
Molecular and Cellular Biology
  • Wim de Lau, University Medical Center Utrecht
  • Pekka Kujala, Antoni van Leeuwenhoek Ziekenhuis
  • Kerstin Schneeberger, Wilhelmina Kinderziekenhuis
  • Sabine Middendorp, Wilhelmina Kinderziekenhuis
  • Vivian S.W. Li, University Medical Center Utrecht
  • Nick Barker, University Medical Center Utrecht
  • Anton Martens, University Medical Center Utrecht
  • Frans Hofhuis, University Medical Center Utrecht
  • Rodney P. DeKoter, Schulich School of Medicine & Dentistry
  • Peter J. Peters, Antoni van Leeuwenhoek Ziekenhuis
  • Edward Nieuwenhuis, Wilhelmina Kinderziekenhuis
  • Hans Clevers, University Medical Center Utrecht
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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. © 2012, American Society for Microbiology.

Citation Information
Wim de Lau, Pekka Kujala, Kerstin Schneeberger, Sabine Middendorp, et al.. "Peyer's patch M cells derived from Lgr5+ stem cells require SpiB and are induced by RankL in cultured miniguts" Molecular and Cellular Biology Vol. 32 Iss. 18 (2012) p. 3639 - 3647
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