Determinants of the epithelial-muscular axis on embryonic stem cell-derived gut-like structures.
Dome-like structures with epithelial-muscular layers resembling the gut have been derived from mouse embryonic stem (ES) cells. These domes have been reported to show spontaneous contractions and are called ES gut. In the present study, we examined the epithelial-muscular axis of these domes by detecting differentiation markers. A normal epithelial-muscular axis was exhibited in the domes with spontaneous motility, whereas the domes without spontaneous motility showed either an inverted or obscure axis. To investigate the factors affecting the epithelial-muscular axis, we examined the expression of hedgehog signaling factors in the domes. Expression of hedgehog family factors was detected in the epithelial components of the domes with motility, whereas this expression was inverted or obscure in the domes without motility. Out of the 25 domes, 10 of the 10 motility (+) domes showed a normal epithelial-muscular axis, whereas 14 of the 15 motility (-) domes lacked a normal epithelial-muscular axis. This implies that activin A upregulated the expression of sonic hedgehog and intestinal alkaline phosphatase in the embryoid bodies. These findings suggest that the motility of the ES gut depends on the domes' epithelial-muscular axis.
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
Yi
Y
Luo
Miyako
M
Takaki
Hiromi
H
Misawa
Hiroko
H
Matsuyoshi
Tomonori
T
Sasahira
Yoshitomo
Y
Chihara
Kiyomu
K
Fujii
Hitoshi
H
Ohmori
Hiroki
H
Kuniyasu
D028341:Activins / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D058732:Embryoid Bodies / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; D053823:Hedgehog Proteins; C422405:activin A; D028341:Activins; D000469:Alkaline Phosphatase