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Abstract
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.
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