Variable allelic expression of imprinted genes in human pluripotent stem cells during differentiation into specialized cell types in vitro |
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| Authors: | Sang-Wook Park Jihoon Kim Jong-Lyul Park Ji-Yun Ko Ilkyun Im Hyo-Sang Do Hyemin Kim Ngoc-Tung Tran Sang-Hun Lee Yong Sung Kim Yee Sook Cho Dong Ryul Lee Yong-Mahn Han |
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| Institution: | 1. Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea;2. Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea;3. Functional Genomics Research Center,Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea;4. Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea;5. Fertility Center, CHA Gangnam Medical Center, CHA University, 606-5 Yeoksam-dong, Gangnam-gu, Seoul 135-081, Republic of Korea |
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| Abstract: | Genomic imprinting is an epigenetic phenomenon by which a subset of genes is asymmetrically expressed in a parent-of-origin manner. However, little is known regarding the epigenetic behaviors of imprinted genes during human development. Here, we show dynamic epigenetic changes in imprinted genes in hESCs during in vitro differentiation into specialized cell types. Out of 9 imprinted genes with single nucleotide polymorphisms, mono-allelic expression for three imprinted genes (H19, KCNQ1OT1, and IPW), and bi- or partial-allelic expression for three imprinted genes (OSBPL5, PPP1R9A, and RTL1) were stably retained in H9-hESCs throughout differentiation, representing imprinting stability. Three imprinted genes (KCNK9, ATP10A, and SLC22A3) showed a loss and a gain of imprinting in a lineage-specific manner during differentiation. Changes in allelic expression of imprinted genes were observed in another hESC line during in vitro differentiation. These findings indicate that the allelic expression of imprinted genes may be vulnerable in a lineage-specific manner in human pluripotent stem cells during differentiation. |
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| Keywords: | Human pluripotent stem cells In vitro differentiation Imprinted genes Allele-specific expression |
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