TY - JOUR
T1 - Liver maturation deficiency in p57Kip2-/- mice occurs in a hepatocytic p57Kip2 expression-independent manner
AU - Yanagida, Ayaka
AU - Chikada, Hiromi
AU - Ito, Keiichi
AU - Umino, Ayumi
AU - Kato-Itoh, Megumi
AU - Yamazaki, Yuji
AU - Sato, Hideyuki
AU - Kobayashi, Toshihiro
AU - Yamaguchi, Tomoyuki
AU - Nakayama, Keiichi I.
AU - Nakauchi, Hiromitsu
AU - Kamiya, Akihide
N1 - Funding Information:
The Education and Research Support Center of Tokai University assisted with some of the analyses. We thank Dr. Kasai (The Institute of Medical Science, The University of Tokyo) for critically reading the manuscript. Dr. KI Nakayama generated the p57 Kip2 -deficient mouse line. Dr. A. Yanagida, Dr. M. Kato-Itoh, Ms. A. Umino, Mr. H. Sato, and Dr. T. Kobayahi performed chimeric mouse experiments. Mr. Y. Yamazaki performed flow cytometry. Dr. A. Yanagida, Dr. K. Ito, and Dr. H. Chikada performed gene expression analyses of the fetal liver cells and instructive discussions. Dr. A. Yanagida, Dr. A. Kamiya and Dr. H. Nakauchi conceived the project and designed the experiments and wrote the manuscript. This work was supported by a Grant-in-Aid for JSPS Fellows and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology , Japan ( 13J05787 for AY, 26293178 and 25670373 for AK).
PY - 2015/11/15
Y1 - 2015/11/15
N2 - 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 p57Kip2-/- 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, p57Kip2-/- hepatoblasts could differentiate into mature hepatocytes in p57Kip2-/- and WT chimeric mice, suggesting that the intrinsic activity of p57Kip2 does not simply regulate hepatoblast maturation.
AB - 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 p57Kip2-/- 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, p57Kip2-/- hepatoblasts could differentiate into mature hepatocytes in p57Kip2-/- and WT chimeric mice, suggesting that the intrinsic activity of p57Kip2 does not simply regulate hepatoblast maturation.
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U2 - 10.1016/j.ydbio.2015.07.004
DO - 10.1016/j.ydbio.2015.07.004
M3 - Article
C2 - 26165599
AN - SCOPUS:84952863561
VL - 407
SP - 331
EP - 343
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -