Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10931411 | Developmental Biology | 2015 | 13 Pages |
Abstract
Fetal hepatic stem/progenitor cells, hepatoblasts, are highly proliferative cells and the source of both hepatocytes and cholangiocytes. In contrast, mature hepatocytes have a low proliferative potency and high metabolic functions. Cell proliferation is regulated by cell cycle-related molecules. However, the correlation between cell cycle regulation and hepatic maturation are still unknown. To address this issue, we revealed that the cell cycle inhibitor p57Kip2 was expressed in the hepatoblasts and mesenchymal cells of fetal liver in a spatiotemporal manner. In addition, we found that hepatoblasts in p57Kip2â/â mice were highly proliferative and had deficient maturation compared with those in wild-type (WT) mice. However, there were no remarkable differences in the expression levels of cell cycle- and bipotency-related genes except for Ccnd2. Furthermore, p57Kip2â/â hepatoblasts could differentiate into mature hepatocytes in p57Kip2â/â and WT chimeric mice, suggesting that the intrinsic activity of p57Kip2 does not simply regulate hepatoblast maturation.
Keywords
PDGFRRT-PCRFGFDAPIPFAWntGAPDHTLDATaqMan low density arrayGFPMEFIMDMOSMCyPwingless-type MMTV integration site familyHPRT1CKIDOXFBSDMEMDlk1PBSLhx2hepatoblastLIFHSCGMEM4′,6-diamidino-2-phenylindole dihydrochlorideC/EBPαCCAAT/enhancer-binding protein αHnfDulbecco's modified Eagle's mediumIscove's modified Dulbecco's mediumα-fetoproteinstandard deviationoncostatin MTATAFPTyrosine aminotransferasedoxycyclineDelta-like 1 homologDevelopmentembryonic dayfetal bovine serumES celliPS cellHematopoietic stem cellEmbryonic stem cellInduced pluripotent stem cellcytokeratinCytochrome P450leukemia inhibitory factorhepatocyte nuclear factorfibroblast growth factorFoxaPhosphate-buffered salineBMPcyclin-dependent kinase inhibitormouse embryonic fibroblastknockoutwild-typeHypoxanthine phosphoribosyltransferase 1reverse transcription-polymerase chain reactionpolymerase chain reactionPCRparaformaldehydegreen fluorescent proteinbone morphogenic proteinsCell cycleglyceraldehyde 3-phosphate dehydrogenaseplatelet-derived growth factor receptor
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Authors
Ayaka Yanagida, Hiromi Chikada, Keiichi Ito, Ayumi Umino, Megumi Kato-Itoh, Yuji Yamazaki, Hideyuki Sato, Toshihiro Kobayashi, Tomoyuki Yamaguchi, Keiichi I. Nakayama, Hiromitsu Nakauchi, Akihide Kamiya,