Studies on genomic imprinting status in hESCs during neuronal differentiation인간배아줄기세포의 신경세포로의 분화 과정에서 유전자각인 상태 연구

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It has been reported that the epigenetic status of imprinted genes are predominantly stable in undifferentiated human embryonic stem cells (hESCs) and embryoid bodies (EBs) derived from hESCs. However, much less is known about the gene expression patterns and the epigenetic status of imprinted genes during differentiation of hESCs into a specified cell type. In this study, the temporal expression and epigenetic status of imprinted genes were examined in hESCs undergoing neuronal differentiation, and in doing so, to help understand tissue-specific imprinting. Out of 30 imprinted genes examined, many imprinted genes exhibited dynamic expression profiles during differentiation. Thus, transcription of imprinted genes during differentiation of hESCs seemed to be regulated in a gene-dependent manner rather than in a cluster-dependent manner. In addition, the allele-specific expression of 12 imprinted genes was examined. Only three genes were demonstrably monoallelic. We also found that seven genes showed either biallelic or partial-allelic expression in hESCs during differentiation. Interestingly, two imprinted genes PON1 and SLC22A3 shifted from biallelic expression in hESCs to partial-allelic expression in neural precursors (NP) cells and dopaminergic (DA) neurons, providing evidence of tissue-specific imprinting. Differential methylation at each of the imprinting control loci analyzed was re-tained throughout differentiation of hESCs to the neuronal lineage, including regions that contained biallelically expressed genes. This suggests that DNA methylation is not responsible for temporal and allele-specific expression of imprinted genes. This study will provide an in vitro model for understanding epigenetic behaviors of imprinted genes during human post-implantation development.
Advisors
Han, Yong-Mahnresearcher한용만researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2011
Identifier
466362/325007  / 020047149
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2011.2, [ vii, 124 p. ]

Keywords

후성유전학; 신경세포 분화; 유전자각인; hESCs; neuronal differentiation; epigenetics; genomic imprinting; 인간배아줄기세포

URI
http://hdl.handle.net/10203/27717
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=466362&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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