Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue.
The importance of asymmetric divisions for stem cell function and maintenance is well established in the developing nervous system and the skin; however, its role in gut epithelium and its importance for tumorigenesis is still debated. We demonstrate alignment of mitotic spindles perpendicular to the apical surface specifically in the stem cell compartments of mouse and human intestine and colon. This orientation correlates with the asymmetric retention of label-retaining DNA. Both the preference for perpendicular spindle alignment and asymmetric label retention are lost in precancerous tissue heterozygous for the adenomatous polyposis coli tumor suppressor (Apc). This loss correlates with cell shape changes specifically in the stem cell compartment. Our data suggest that loss of asymmetric division in stem cells might contribute to the oncogenic effect of Apc mutations in gut epithelium.
Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH, UK.
Aaron J
AJ
Quyn
Paul L
PL
Appleton
Francis A
FA
Carey
Robert J C
RJ
Steele
Nick
N
Barker
Hans
H
Clevers
Rachel A
RA
Ridgway
Owen J
OJ
Sansom
Inke S
IS
Näthke
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D048430:Cell Shape; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008941:Spindle Apparatus / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein