title: The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
abstract: Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. Thus, Hes1-null ES cells display less heterogeneity in both the differentiation timing and fate choice, suggesting that the cyclic gene Hes1 contributes to heterogeneous responses of ES cells even under the same environmental conditions.
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan. tkobayas@virus.kyoto-u.ac.jp
authors.forename: Taeko
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizuno
authors.forename: Itaru
authors.initials: I
authors.lastname: Imayoshi
authors.forename: Chikara
authors.initials: C
authors.lastname: Furusawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology; D051880:Receptors, Notch / Q000378:metabolism; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1313-8
references.pmid: 16432209
references.citation: Cell Stem Cell. 2008 Oct 9;3(4):391-401
references.pmid: 18940731
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11292-7
references.pmid: 17592117
references.citation: Curr Opin Genet Dev. 2001 Oct;11(5):587-94
references.pmid: 11532403
references.citation: Development. 2007 Aug;134(16):2895-902
references.pmid: 17660198
references.citation: Neuron. 2008 Apr 10;58(1):52-64
references.pmid: 18400163
references.citation: Development. 2007 Apr;134(7):1243-51
references.pmid: 17329370
references.citation: Nature. 2007 Dec 20;450(7173):1230-4
references.pmid: 18097409
references.citation: J Cell Physiol. 2002 Sep;192(3):327-38
references.pmid: 12124778
references.citation: Stem Cells. 2007 Oct;25(10):2534-42
references.pmid: 17615266
references.citation: Development. 2008 Sep;135(18):3113-24
references.pmid: 18725516
references.citation: Methods Mol Biol. 2004;246:429-38
references.pmid: 14970608
references.citation: PLoS Biol. 2006 May;4(5):e121
references.pmid: 16594731
references.citation: Nucleic Acids Res. 2006 Mar 17;34(5):e42
references.pmid: 16547197
references.citation: Circ Res. 2006 Jun 23;98(12):1471-8
references.pmid: 16690879
references.citation: Cell Stem Cell. 2008 Nov 6;3(5):480-3
references.pmid: 18983963
references.citation: Cell. 2003 Oct 31;115(3):281-92
references.pmid: 14636556
references.citation: Nature. 2003 May 29;423(6939):541-5
references.pmid: 12774123
references.citation: Nature. 2008 May 22;453(7194):544-7
references.pmid: 18497826
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1292-6
references.pmid: 7877970
references.citation: Annu Rev Cell Dev Biol. 2001;17:435-62
references.pmid: 11687496
references.citation: J Theor Biol. 2001 Apr 21;209(4):395-416
references.pmid: 11319890
references.citation: Science. 2002 Oct 25;298(5594):840-3
references.pmid: 12399594
references.citation: Nature. 2008 Feb 14;451(7180):796-801
references.pmid: 18235444
references.citation: Biochem Biophys Res Commun. 2008 Jul 18;372(1):142-6
references.pmid: 18477475
references.citation: Cell. 2008 Feb 22;132(4):661-80
references.pmid: 18295582
references.citation: Nat Protoc. 2007;2(3):739-52
references.pmid: 17406636
references.citation: Methods Enzymol. 2003;365:327-41
references.pmid: 14696356
references.citation: Development. 2008 Mar;135(5):909-18
references.pmid: 18263842