Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.
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.
Liu
Lei
L
State Key Laboratory of Reproductive Biology, Institute of Zoology, ChineseAcademy of Sciences, Beijing 100101, China.
Luo
Guan-Zheng
GZ
Yang
Wei
W
Zhao
Xiaoyang
X
Zheng
Qinyuan
Q
Lv
Zhuo
Z
Li
Wei
W
Wu
Hua-Jun
HJ
Wang
Liu
L
Wang
Xiu-Jie
XJ
Zhou
Qi
Q
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*
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
Nature. 2009 Jul 2;460(7251):118-22
19571885
Science. 2002 Nov 1;298(5595):1039-43
12351676
Nat Biotechnol. 2007 Oct;25(10):1177-81
17724450
Nature. 2007 Jul 19;448(7151):318-24
17554336
Genes Dev. 2002 Nov 15;16(22):2893-905
12435631
Cell. 2008 Feb 22;132(4):532-6
18295569
Stem Cells. 2008 Jun;26(6):1496-505
18403752
PLoS Biol. 2008 Oct 21;6(10):e253
18942890
Cell Stem Cell. 2009 Jul 2;5(1):111-23
19570518
PLoS Biol. 2008 Jun 3;6(6):e135
18532878
Philos Trans R Soc Lond B Biol Sci. 2008 Jun 27;363(1500):2079-87
18375377
Cell. 2009 Jan 23;136(2):364-77
19167336
Cell. 2006 Aug 25;126(4):663-76
16904174
Nat Protoc. 2009;4(1):44-57
19131956
Cell Cycle. 2008 Apr 1;7(7):885-91
18414030
Genomics. 2006 Feb;87(2):225-35
16309881
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-8
8378314
Mutat Res. 2008 Dec 1;647(1-2):21-9
18723033
Development. 2009 Feb;136(4):509-23
19168672
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4335-40
20160098
Genome Res. 2004 Sep;14(9):1741-8
15310658
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W358-63
18487275
Nature. 2009 Sep 3;461(7260):86-90
19672241