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

Mol Cell Biol. 2012 Sep;32(18):3639-47. doi: 10.1128/MCB.00434-12. Epub 2012 Jul 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / biosynthesis
  • Embryonic Development
  • Green Fluorescent Proteins / genetics
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Intestines / embryology
  • Mice
  • Mice, Knockout
  • Peyer's Patches / cytology*
  • Peyer's Patches / embryology
  • Peyer's Patches / metabolism*
  • Proto-Oncogene Proteins c-ets / metabolism*
  • RANK Ligand / metabolism*
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Stem Cells / metabolism
  • Transcription Factors / biosynthesis


  • DNA-Binding Proteins
  • Lgr5 protein, mouse
  • Proto-Oncogene Proteins c-ets
  • RANK Ligand
  • Receptors, G-Protein-Coupled
  • Spi-B protein, mouse
  • Tnfsf11 protein, mouse
  • Transcription Factors
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins