title: Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells.
abstract: Mouse embryonic stem cell (ESC) cultures exhibit a heterogeneous mixture of metastable cells sporadically entering the 2-cell (2C)-embryo-like state, critical for ESC potency. One of 2-cell genes, Zscan4, has been shown to be responsible for telomere maintenance, genomic stability and pluripotency of mouse ESCs. Functions of other 2C-genes in ESCs remain elusive. Here we show that 2C-genes Tcstv1 and Tcstv3 play a role in regulation of telomere lengths. Overexpression or knockdown Tcstv1 and Tcstv3 does not immediately affect proliferation, pluripotency and differentiation in vitro of ESCs. However, ectopic expression of Tcstv1 or Tcstv3 results in telomere elongation, whereas Tcstv1/3 knockdown shortens telomeres of ESCs. Overexpression of Tcstv1 or Tcstv3 does not alter telomere stability. Furthermore, Tcstv1 can increase Zscan4 protein levels and telomere recombination by telomere sister chromatid exchange (T-SCE). Depletion of Tcstv1/3 reduces Zscan4 protein levels. Together, Tcstv1 and Tcstv3 are involved in telomere maintenance that is required for long-term self-renewal of mouse ESCs. Our data also suggests that Tcstv1/3 may co-operate and stabilize Zscan4 protein but the molecular bases remain to be determined.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jiameng
authors.initials: J
authors.lastname: Dan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Renpeng
authors.initials: R
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiawei
authors.initials: X
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology; 2011 Collaborative Innovation Center for Biotherapy, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000502:physiology*
references.citation: Nat Commun. 2013;4:1966
references.pmid: 23739662
references.citation: Nucleic Acids Res. 2004;32(12):3743-51
references.pmid: 15258249
references.citation: Sci Rep. 2013;3:3492
references.pmid: 24336466
references.citation: PLoS One. 2014;9(1):e83235
references.pmid: 24392082
references.citation: Stem Cells Dev. 2014 Apr 1;23(7):779-89
references.pmid: 24083387
references.citation: Dev Cell. 2014 Apr 14;29(1):7-19
references.pmid: 24735877
references.citation: Cell Rep. 2014 Dec 11;9(5):1603-9
references.pmid: 25464850
references.citation: Sci Rep. 2015;5:9146
references.pmid: 25772165
references.citation: Dev Biol. 2007 Jul 15;307(2):539-50
references.pmid: 17553482
references.citation: Dev Biol. 2004 Aug 15;272(2):483-96
references.pmid: 15282163
references.citation: Dev Cell. 2004 Oct;7(4):597-606
references.pmid: 15469847
references.citation: Nature. 1981 Jul 9;292(5819):154-6
references.pmid: 7242681
references.citation: Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8
references.pmid: 6950406
references.citation: Cell. 1987 Dec 24;51(6):887-98
references.pmid: 3319189
references.citation: Nature. 1990 Mar 8;344(6262):126-32
references.pmid: 1689810
references.citation: Cytogenet Cell Genet. 1993;63(2):126-7
references.pmid: 8467711
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-8
references.pmid: 8378314
references.citation: Mutagenesis. 1996 Mar;11(2):139-44
references.pmid: 8671729
references.citation: Cell. 1997 Oct 3;91(1):25-34
references.pmid: 9335332
references.citation: J Cell Biol. 1999 Feb 22;144(4):589-601
references.pmid: 10037783
references.citation: Cytometry. 1999 Aug 1;36(4):267-78
references.pmid: 10404142
references.citation: Gene Expr Patterns. 2006 Jan;6(2):213-24
references.pmid: 16325481
references.citation: Comp Med. 2006 Feb;56(1):17-22
references.pmid: 16521855
references.citation: Nucleic Acids Res. 2006;34(17):4780-90
references.pmid: 16971461
references.citation: Cell Res. 2013 Jan;23(1):92-106
references.pmid: 23147797
references.citation: Nat Rev Genet. 2007 Apr;8(4):299-309
references.pmid: 17363977
references.citation: Reprod Fertil Dev. 2015 Mar;27(3):557-66
references.pmid: 24524188
references.citation: Nat Cell Biol. 2007 Dec;9(12):1436-41
references.pmid: 17982445
references.citation: Cell. 2008 Feb 22;132(4):567-82
references.pmid: 18295576
references.citation: Annu Rev Genet. 2008;42:301-34
references.pmid: 18680434
references.citation: Cell Stem Cell. 2009 Feb 6;4(2):141-54
references.pmid: 19200803
references.citation: Stem Cells. 2009 Sep;27(9):2136-45
references.pmid: 19544532
references.citation: Science. 2009 Nov 13;326(5955):948-52
references.pmid: 19965504
references.citation: Nature. 2010 Apr 8;464(7290):858-63
references.pmid: 20336070
references.citation: Cell Res. 2011 May;21(5):779-92
references.pmid: 21283131
references.citation: Cell Res. 2012 Apr;22(4):757-68
references.pmid: 22184006
references.citation: Nature. 2012 Jul 5;487(7405):57-63
references.pmid: 22722858
references.citation: Cell. 2001 Sep 21;106(6):661-73
references.pmid: 11572773
references.citation: Oncogene. 2002 Jan 21;21(4):553-63
references.pmid: 11850780
references.citation: Curr Biol. 2003 Sep 2;13(17):1549-56
references.pmid: 12956959
references.citation: DNA Res. 2013 Aug;20(4):391-402
references.pmid: 23649898