title: Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells.
abstract: Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED-HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration.
authors: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, 200025 Shanghai, China.
authors: An
authors: A
authors: Zeng
authors: Yong-Qin
authors: YQ
authors: Li
authors: Chen
authors: C
authors: Wang
authors: Xiao-Shuai
authors: XS
authors: Han
authors: Ge
authors: G
authors: Li
authors: Jian-Yong
authors: JY
authors: Wang
authors: Dang-Sheng
authors: DS
authors: Li
authors: Yong-Wen
authors: YW
authors: Qin
authors: Yufang
authors: Y
authors: Shi
authors: Gary
authors: G
authors: Brewer
authors: Qing
authors: Q
authors: Jing
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D015801:Helminth Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D010932:Planarians / Q000166:cytology* / Q000502:physiology; D021381:Protein Transport; D034622:RNA Interference; D012038:Regeneration; D059467:Transcriptome
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D015801:Helminth Proteins; D000090266:Chromobox Protein Homolog 5
references: Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11861-5
references: 12917490
references: Curr Opin Genet Dev. 2000 Apr;10(2):204-10
references: 10753776
references: Cell. 2000 Jan 7;100(1):157-68
references: 10647940
references: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18491-6
references: 16344473
references: Curr Opin Genet Dev. 2008 Apr;18(2):169-74
references: 18329871
references: Genome Biol. 2007;8(4):R62
references: 17445279
references: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18467-72
references: 16339308
references: Genome Biol. 2012;13(3):R19
references: 22439894
references: Dev Biol. 2012 May 15;365(2):458-69
references: 22445864
references: Science. 2005 Nov 25;310(5752):1327-30
references: 16311336
references: Genes Dev. 2010 Sep 15;24(18):2081-92
references: 20844018
references: Cell Res. 2011 Aug;21(8):1172-81
references: 21606950
references: Nature. 2001 Mar 1;410(6824):116-20
references: 11242053
references: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8242-7
references: 20404188
references: Oncotarget. 2011 Oct;2(10):783-96
references: 21998152
references: Genes Dev. 2012 May 1;26(9):988-1002
references: 22549959
references: Dev Dyn. 2009 Feb;238(2):443-50
references: 19161223
references: Cell. 1998 Jan 9;92(1):105-16
references: 9489704
references: J Cell Sci. 2010 Mar 1;123(Pt 5):690-8
references: 20124416
references: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5901-6
references: 17376870
references: Nucleic Acids Res. 2005 May 19;33(9):2852-8
references: 15905474
references: Nat Cell Biol. 2006 May;8(5):532-8
references: 16570078
references: Annu Rev Cell Dev Biol. 2004;20:725-57
references: 15473858
references: Science. 2008 Mar 28;319(5871):1791-2
references: 18369138
references: EMBO J. 1999 Nov 15;18(22):6385-95
references: 10562550
references: Nature. 2007 Aug 2;448(7153):553-60
references: 17603471
references: Development. 2005 Apr;132(8):1863-74
references: 15772127
references: J Embryol Exp Morphol. 1984 Oct;83:63-80
references: 6502076
references: EMBO J. 2012 Jun 13;31(12):2755-69
references: 22543868
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D599-606
references: 17881371
references: Dev Cell. 2006 Aug;11(2):159-69
references: 16890156
references: Cell. 2006 Jan 27;124(2):241-5
references: 16439195
references: Bioinformatics. 2004 Nov 22;20(17):3246-8
references: 15180930
references: J Cell Sci. 2007 Oct 1;120(Pt 19):3425-35
references: 17855381
references: Development. 2010 Apr;137(8):1231-41
references: 20223763
references: Cell. 2006 Apr 21;125(2):315-26
references: 16630819
references: Genes Dev. 2004 Sep 1;18(17):2147-60
references: 15342492
references: Nature. 2001 Mar 1;410(6824):120-4
references: 11242054
references: EMBO Rep. 2011 Mar;12(3):208-15
references: 21311559
references: Dev Biol. 2010 Feb 1;338(1):76-85
references: 19766622
references: Dev Biol. 2000 Apr 15;220(2):142-53
references: 10753506
references: Development. 2005 Aug;132(16):3691-703
references: 16033796
references: Cell Res. 2011 Dec;21(12):1750-4
references: 21894189
references: Nat Rev Mol Cell Biol. 2004 Apr;5(4):296-304
references: 15071554
references: Stem Cells. 2012 Aug;30(8):1734-45
references: 22696458
references: Nat Rev Mol Cell Biol. 2011 Jan;12(1):36-47
references: 21179060
references: Nat Rev Genet. 2007 Jan;8(1):35-46
references: 17173056
references: Cell Stem Cell. 2012 Mar 2;10(3):299-311
references: 22385657
references: Dev Biol. 2010 May 15;341(2):429-43
references: 20230812
references: EMBO J. 2007 Aug 8;26(15):3616-28
references: 17627279
references: Dev Dyn. 2000 Aug;218(4):603-14
references: 10906779
references: PLoS Genet. 2006 Nov 3;2(11):e181
references: 17083276
references: Science. 2011 May 13;332(6031):811-6
references: 21566185
references: Cell. 2008 Jul 11;134(1):162-74
references: 18614019
references: Cell. 2011 Jun 10;145(6):835-50
references: 21663790
references: Dev Growth Differ. 2006 Aug;48(6):371-80
references: 16872450
references: Nat Protoc. 2006;1(2):729-48
references: 17406303
references: Annu Rev Genet. 2009;43:467-92
references: 19919324
references: Dev Biol. 2010 Aug 15;344(2):979-91
references: 20599901
references: PLoS Biol. 2010 Oct 12;8(10):e1000509
references: 20967238
references: Dev Dyn. 2008 Nov;237(11):3099-101
references: 18627099
references: Curr Opin Genet Dev. 2003 Oct;13(5):492-6
references: 14550414
references: Nat Rev Genet. 2002 Mar;3(3):210-9
references: 11972158
references: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9923-7
references: 2124708
references: Science. 2010 Jan 29;327(5965):542-5
references: 20110496
references: Cell Stem Cell. 2009 Jan 9;4(1):80-93
references: 19128795
references: J Cell Biol. 2003 May 26;161(4):707-14
references: 12756231
references: Nat Cell Biol. 2006 Mar;8(3):285-92
references: 16462733
references: J Cell Sci. 2012 Apr 1;125(Pt 7):1657-65
references: 22427692
references: Genes Dev. 2010 Oct 1;24(19):2133-45
references: 20889714
references: Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16462-9
references: 12151603
references: Bioessays. 2005 Jan;27(1):17-28
references: 15612037
references: Dev Cell. 2005 May;8(5):635-49
references: 15866156
references: Cell Stem Cell. 2008 Sep 11;3(3):327-39
references: 18786419
references: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5181-6
references: 19279220