title: Variable allelic expression of imprinted genes in human pluripotent stem cells during differentiation into specialized cell types in vitro.
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.
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center,Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Ko
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Ilkyun
authors.initials: I
authors.lastname: Im
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Hyo-Sang
authors.initials: HS
authors.lastname: Do
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Ngoc-Tung
authors.initials: NT
authors.lastname: Tran
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Functional Genomics Research Center,Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Yee Sook
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Fertility Center, CHA Gangnam Medical Center, CHA University, 606-5 Yeoksam-dong, Gangnam-gu, Seoul 135-081, Republic of Korea.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. Electronic address: ymhan@kaist.ac.kr.
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008297:Male; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: Allele-specific expression; Human pluripotent stem cells; Imprinted genes; In vitro differentiation