title: Paneth cells in intestinal homeostasis and tissue injury.
abstract: Adult stem cell niches are often co-inhabited by cycling and quiescent stem cells. In the intestine, lineage tracing has identified Lgr5(+) cells as frequently cycling stem cells, whereas Bmi1(+), mTert(+), Hopx(+) and Lrig1(+) cells appear to be more quiescent. Here, we have applied a non-mutagenic and cell cycle independent approach to isolate and characterize small intestinal label-retaining cells (LRCs) persisting in the lower third of the crypt of Lieberkühn for up to 100 days. LRCs do not express markers of proliferation and of enterocyte, goblet or enteroendocrine differentiation, but are positive for Paneth cell markers. While during homeostasis, LR/Paneth cells appear to play a supportive role for Lgr5(+) stem cells as previously shown, upon tissue injury they switch to a proliferating state and in the process activate Bmi1 expression while silencing Paneth-specific genes. Hence, they are likely to contribute to the regenerative process following tissue insults such as chronic inflammation.
authors: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
authors: Sabrina
authors: S
authors: Roth
authors: Patrick
authors: P
authors: Franken
authors: Andrea
authors: A
authors: Sacchetti
authors: Andreas
authors: A
authors: Kremer
authors: Kurt
authors: K
authors: Anderson
authors: Owen
authors: O
authors: Sansom
authors: Riccardo
authors: R
authors: Fodde
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: C489421:Bmi1 protein, mouse; C493597:Lgr5 protein, mouse; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D063150:Polycomb Repressive Complex 1