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( Minjee Kim ),( Woo Kyun Bae ),( Valentina M Factor ),( Keunsoo Kang ),( Lothar Hennighausen ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: Polycomb group protein enhancer of zeste homolog 2 (EZH2) controls cell proliferation and differentiation and is frequently up-regulated in hepatocellular carcinoma. Genetic inactivation of Ezh2 did not produce obvious phenotypic differences in knockout livers suggesting a functional redundancy with Ezh1 homolog. Methods: To investigate the role of both Ezh1 and Ezh2 in liver homeostasis, we generated double knockout mice (E1/2KO) by crossing Ezh1 null and albumin promoter- driven Ezh2 conditional-null mice.The combined loss of EZH1 and EZH2 in mouse hepatocytes caused a global and gene-specific depletion of H3K27me3 marks including genes associated with hepatocyte homeostasis and regeneration. Mice mutant for both Ezh1 and Ezh2 remained viable and overtly normal by 3 months of age. Thereafter, E1/2KO mice exhibited progressive liver abnormalities manifested by development of regenerative nodules and concomitant periportal fibrosis, infiammatory infiltration and activation of A6-positive hepatic progenitor cells (HPCs). Results: In response to chronic treatment with CCl4, E1/2KO mice showed increased hepatic degeneration associated with liver dysfunction, cholestasis, and reduced ability to proliferate. CCl4-induced hepatotoxicity triggered an activation of HPCs, which did not prevent early lethality of E1/2KO mice. After 2/3ds partial hepatectomy, E1/2KO livers showed an increased liver injury and a blunted regenerative response. RNA-seq analysis revealed dysregulation of genes related to regulation of cell survival, fibrosis, and proliferation including Cdkn2a and Cdkn2b. Conclusions: This work demonstrates a critical role of EZH1 and EZH2in maintaining hepatic homeostasis and ability to regenerate.
Generation of Induced Pluripotent Stem Cells from Mouse Hepatocytic Lineage Cells
Dongho Choi,Kye-Yoon Park,Jeonghoon Heo,Cheul Hyung Cho,Marian Durkin,Agnes Holczbauer,Jens U. Marquardt,Valentina M. Factor,Karim Si-Tayeb,Stephen A. Duncan,Snorri S. Thorgeirsson 한국간담췌외과학회 2010 한국간담췌외과학회 학술대회지 Vol.2010 No.3
총회구연 : 그랜드볼룸 ; 인간배아줄기세포와 인간역분화만능줄기세포의 간세포 분화능에 대한 비교연구 (초)
( Dong Ho Choi ),( Kye Yoon Park ),( Jeon Hoon Heo ),( Cheul Hyung Cho ),( Marian Durkin ),( Agnes Holczbauer ),( Jens U. Marquardt ),( Valentina M. Factor ),( Karim Si Tayeb ),( Stephen A. Duncan ),( 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3(S)
Comparison of Hepatic Differentiation Potential between Human ES and iPS Cells
Dongho Choi,Kye-Yoon Park,Jeonghoon Heo,Cheul Hyung Cho,Marian Durkin,Agnes Holczbauer,Jens U. Marquardt,Valentina M. Factor,Karim Si-Tayeb,Stephen A. Duncan,Snorri S. Thorgeirsson 한국간담췌외과학회 2010 한국간담췌외과학회 학술대회지 Vol.2010 No.3