c-Myb is required for progenitor cell homeostasis in colonic crypts

Jordane Malaterre, Marina Carpinelli, Matthias Ernst, Warren Alexander, Michael Cooke, Susan Sutton, Sebastian Dworkin, Joan K. Heath, Jon Frampton, Grant McArthur, Hans Clevers, Douglas Hilton, Theo Mantamadiotis, Robert G. Ramsay

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

92 Citaten (Scopus)

Samenvatting

The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar, goblet, and endocrine cells. The role of c-Myb in crypt homeostasis has not been elucidated. Here we have studied three genetically distinct hypomorphic c-myb mutant mouse strains, all of which show reduced colonic crypt size. The mutations target the key domains of the transcription factor: the DNA binding, transactivation, and negative regulatory domains. In vivo proliferation and cell cycle marker studies suggest that these mice have a progenitor cell proliferation defect mediated in part by reduced Cyclin E1 expression. To independently assess the extent to which c-myb is required for colonic crypt homeostasis we also generated a novel tissue-specific mouse model to allow the deletion of c-myb in adult colon, and using these mice we show that c-Myb is required for crypt integrity, normal differentiation, and steady-state proliferation.

Originele taal-2Engels
Pagina's (van-tot)3829-3834
Aantal pagina's6
TijdschriftProceedings of the National Academy of Sciences of the United States of America
Volume104
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 6 mrt. 2007
Extern gepubliceerdJa

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