title: Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.
abstract: Low reprogramming efficiency and reduced pluripotency have been the two major obstacles in induced pluripotent stem (iPS) cell research. An effective and quick method to assess the pluripotency levels of iPS cells at early stages would significantly increase the success rate of iPS cell generation and promote its applications. We have identified a conserved imprinted region of the mouse genome, the Dlk1-Dio3 region, which was activated in fully pluripotent mouse stem cells but repressed in partially pluripotent cells. The degree of activation of this region was positively correlated with the pluripotency levels of stem cells. A mammalian conserved cluster of microRNAs encoded by this region exhibited significant expression differences between full and partial pluripotent stem cells. Several microRNAs from this cluster potentially target components of the polycomb repressive complex 2 (PRC2) and may form a feedback regulatory loop resulting in the expression of all genes and non-coding RNAs encoded by this region in full pluripotent stem cells. No other genomic regions were found to exhibit such clear expression changes between cell lines with different pluripotency levels; therefore, the Dlk1-Dio3 region may serve as a marker to identify fully pluripotent iPS or embryonic stem cells from partial pluripotent cells. These findings also provide a step forward toward understanding the operating mechanisms during reprogramming to produce iPS cells and can potentially promote the application of iPS cells in regenerative medicine and cancer therapy.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, ChineseAcademy of Sciences, Beijing 100101, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Guan-Zheng
authors.initials: GZ
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Zheng
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lv
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Wu
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D016000:Cluster Analysis; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D022661:RNA, Untranslated / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D022661:RNA, Untranslated; D007453:Iodide Peroxidase
references.citation: Nature. 2009 Jul 2;460(7251):118-22
references.pmid: 19571885
references.citation: Science. 2002 Nov 1;298(5595):1039-43
references.pmid: 12351676
references.citation: Nat Biotechnol. 2007 Oct;25(10):1177-81
references.pmid: 17724450
references.citation: Nature. 2007 Jul 19;448(7151):318-24
references.pmid: 17554336
references.citation: Genes Dev. 2002 Nov 15;16(22):2893-905
references.pmid: 12435631
references.citation: Cell. 2008 Feb 22;132(4):532-6
references.pmid: 18295569
references.citation: Stem Cells. 2008 Jun;26(6):1496-505
references.pmid: 18403752
references.citation: PLoS Biol. 2008 Oct 21;6(10):e253
references.pmid: 18942890
references.citation: Cell Stem Cell. 2009 Jul 2;5(1):111-23
references.pmid: 19570518
references.citation: PLoS Biol. 2008 Jun 3;6(6):e135
references.pmid: 18532878
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Jun 27;363(1500):2079-87
references.pmid: 18375377
references.citation: Cell. 2009 Jan 23;136(2):364-77
references.pmid: 19167336
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Cell Cycle. 2008 Apr 1;7(7):885-91
references.pmid: 18414030
references.citation: Genomics. 2006 Feb;87(2):225-35
references.pmid: 16309881
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-8
references.pmid: 8378314
references.citation: Mutat Res. 2008 Dec 1;647(1-2):21-9
references.pmid: 18723033
references.citation: Development. 2009 Feb;136(4):509-23
references.pmid: 19168672
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4335-40
references.pmid: 20160098
references.citation: Genome Res. 2004 Sep;14(9):1741-8
references.pmid: 15310658
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W358-63
references.pmid: 18487275
references.citation: Nature. 2009 Sep 3;461(7260):86-90
references.pmid: 19672241