title: Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis.
abstract: During the transition from the inner cell mass (ICM) cells of blastocysts to pluripotent embryonic stem cells (ESCs) in vitro, a normal developmental program is replaced in cells that acquire a capacity for infinite self-renewal and pluripotency. We explored the underlying mechanism of this switch by using RNA-Seq transcriptome analysis at the resolution of single cells. We detected significant molecular transitions and major changes in transcript variants, which include genes for general metabolism. Furthermore, the expression of repressive epigenetic regulators increased with a concomitant decrease in gene activators that might be necessary to sustain the inherent plasticity of ESCs. Furthermore, we detected changes in microRNAs (miRNAs), with one set that targets early differentiation genes while another set targets pluripotency genes to maintain the unique ESC epigenotype. Such genetic and epigenetic events may contribute to a switch from a normal developmental program in adult cells during the formation of diseased tissues, including cancers.
authors.affiliation: Wellcome Trust/Cancer Research, UK.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.forename: Catalin
authors.initials: C
authors.lastname: Barbacioru
authors.forename: Siqin
authors.initials: S
authors.lastname: Bao
authors.forename: Caroline
authors.initials: C
authors.lastname: Lee
authors.forename: Ellen
authors.initials: E
authors.lastname: Nordman
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Kaiqin
authors.initials: K
authors.lastname: Lao
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: D035683:MicroRNAs
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: Nat Genet. 2007 Mar;39(3):380-5
references.pmid: 17259983
references.citation: Cell Stem Cell. 2008 Aug 7;3(2):182-95
references.pmid: 18682240
references.citation: Development. 2007 Mar;134(6):1123-32
references.pmid: 17287250
references.citation: Development. 2005 Jan;132(2):227-33
references.pmid: 15623802
references.citation: Development. 2007 Aug;134(16):2895-902
references.pmid: 17660198
references.citation: Nat Genet. 2006 Apr;38(4):431-40
references.pmid: 16518401
references.citation: Nature. 2007 Dec 20;450(7173):1230-4
references.pmid: 18097409
references.citation: BMC Genomics. 2008 Jun 03;9:269
references.pmid: 18522731
references.citation: Science. 2008 Apr 4;320(5872):97-100
references.pmid: 18292307
references.citation: Cell. 2007 Dec 14;131(6):1109-23
references.pmid: 18083101
references.citation: Genes Dev. 1998 Nov 15;12(22):3579-90
references.pmid: 9832509
references.citation: Development. 2007 Aug;134(16):2889-94
references.pmid: 17660197
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Cell Cycle. 2008 Apr 1;7(7):885-91
references.pmid: 18414030
references.citation: Mol Cell. 2008 Nov 21;32(4):491-502
references.pmid: 19026780
references.citation: Nature. 1981 Jul 9;292(5819):154-6
references.pmid: 7242681
references.citation: Nature. 2008 May 22;453(7194):519-23
references.pmid: 18497825
references.citation: Cell. 2003 Oct 31;115(3):281-92
references.pmid: 14636556
references.citation: Nat Rev Mol Cell Biol. 2009 Feb;10(2):116-25
references.pmid: 19165214
references.citation: Nature. 2003 May 29;423(6939):541-5
references.pmid: 12774123
references.citation: Nat Methods. 2008 Jul;5(7):613-9
references.pmid: 18516046
references.citation: Nature. 2009 Oct 29;461(7268):1292-5
references.pmid: 19816418
references.citation: Nat Protoc. 2006;1(3):1154-9
references.pmid: 17406397
references.citation: Science. 2009 May 15;324(5929):930-5
references.pmid: 19372391
references.citation: Curr Opin Genet Dev. 2006 Oct;16(5):447-54
references.pmid: 16919449
references.citation: Development. 2009 Oct;136(19):3215-22
references.pmid: 19710168
references.citation: Development. 1999 Feb;126(4):723-32
references.pmid: 9895320
references.citation: Science. 2005 Sep 2;309(5740):1519-24
references.pmid: 16141061
references.citation: Biochem Biophys Res Commun. 2008 Mar 21;367(4):899-905
references.pmid: 18194669
references.citation: Cell. 2003 May 30;113(5):631-42
references.pmid: 12787504
references.citation: Development. 1996 Mar;122(3):881-94
references.pmid: 8631266
references.citation: Cell. 2008 Jun 13;133(6):1106-17
references.pmid: 18555785
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Nat Protoc. 2010 Mar;5(3):516-35
references.pmid: 20203668
references.citation: Development. 2007 Feb;134(4):635-46
references.pmid: 17215298
references.citation: Dev Biol. 2008 Jan 15;313(2):614-29
references.pmid: 18067887
references.citation: Genes Dev. 2002 Apr 1;16(7):784-9
references.pmid: 11937486
references.citation: Nat Genet. 2003 Nov;35(3):215-7
references.pmid: 14528307
references.citation: Nat Cell Biol. 2006 Mar;8(3):285-92
references.pmid: 16462733
references.citation: Mol Cell Biol. 2008 Oct;28(20):6426-38
references.pmid: 18710938
references.citation: Stem Cells. 2007 Dec;25(12):2996-3004
references.pmid: 17717068
references.citation: Nat Rev Mol Cell Biol. 2009 Nov;10(11):741-54
references.pmid: 19773805
references.citation: Cell. 2008 Oct 31;135(3):449-61
references.pmid: 18984157
references.citation: Genome Biol. 2003;5(1):R1
references.pmid: 14709173
references.citation: Genes Dev. 2005 Feb 15;19(4):489-501
references.pmid: 15713842
references.citation: J Cell Sci. 2007 Jan 1;120(Pt 1):55-65
references.pmid: 17182901
references.citation: Nat Methods. 2009 May;6(5):377-82
references.pmid: 19349980
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12135-40
references.pmid: 16099834
references.citation: Mol Cell Biol. 2001 Jul;21(13):4330-6
references.pmid: 11390661
references.citation: Cell. 2003 May 30;113(5):643-55
references.pmid: 12787505
references.citation: Nature. 2006 Aug 3;442(7102):533-8
references.pmid: 16767105