Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs.
Animals
Cellular Reprogramming
/ genetics
HEK293 Cells
Humans
Induced Pluripotent Stem Cells
/ cytology
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
/ genetics
Mice
Mice, Knockout
Octamer Transcription Factor-3
/ genetics
Polymerase Chain Reaction
SOXB1 Transcription Factors
/ genetics
Sequence Analysis, RNA
Tetraploidy
Transcription Factors
/ genetics
Klf4
Myc
Oct4
Sox2
Yamanaka cocktail
developmental potential
induced pluripotent stem cells
reprogramming
retroviral silencing
seesaw model of pluripotency
tetraploid complementation
transcription factor
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
05 Dec 2019
05 Dec 2019
Historique:
received:
23
06
2018
revised:
23
08
2019
accepted:
04
10
2019
pubmed:
12
11
2019
medline:
15
9
2020
entrez:
12
11
2019
Statut:
ppublish
Résumé
Oct4 is widely considered the most important among the four Yamanaka reprogramming factors. Here, we show that the combination of Sox2, Klf4, and cMyc (SKM) suffices for reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs). Simultaneous induction of Sox2 and cMyc in fibroblasts triggers immediate retroviral silencing, which explains the discrepancy with previous studies that attempted but failed to generate iPSCs without Oct4 using retroviral vectors. SKM induction could partially activate the pluripotency network, even in Oct4-knockout fibroblasts. Importantly, reprogramming in the absence of exogenous Oct4 results in greatly improved developmental potential of iPSCs, determined by their ability to give rise to all-iPSC mice in the tetraploid complementation assay. Our data suggest that overexpression of Oct4 during reprogramming leads to off-target gene activation during reprogramming and epigenetic aberrations in resulting iPSCs and thereby bear major implications for further development and application of iPSC technology.
Identifiants
pubmed: 31708402
pii: S1934-5909(19)30423-0
doi: 10.1016/j.stem.2019.10.002
pmc: PMC6900749
pii:
doi:
Substances chimiques
KLF4 protein, human
0
Klf4 protein, mouse
0
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Octamer Transcription Factor-3
0
Pou5f1 protein, mouse
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
737-753.e4Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Nature. 2014 Dec 11;516(7530):198-206
pubmed: 25503233
Cell. 2005 Sep 23;122(6):947-56
pubmed: 16153702
Cell Stem Cell. 2008 Mar 6;2(3):230-40
pubmed: 18371448
Cell Stem Cell. 2015 Mar 5;16(3):323-37
pubmed: 25748935
Cell. 2012 Nov 21;151(5):994-1004
pubmed: 23159369
Mol Cell Biol. 2008 Sep;28(17):5420-31
pubmed: 18591257
Nat Genet. 2012 Mar 04;44(4):398-405, S1-2
pubmed: 22387999
Stem Cells. 2009 Mar;27(3):543-9
pubmed: 19096035
Stem Cell Res. 2013 Sep;11(2):861-73
pubmed: 23832110
Cell. 2012 Sep 14;150(6):1209-22
pubmed: 22980981
Cell Stem Cell. 2010 Jul 2;7(1):51-63
pubmed: 20621050
Cell Rep. 2019 Apr 2;27(1):30-39.e4
pubmed: 30943410
Nature. 2009 Oct 1;461(7264):649-3
pubmed: 19718018
J Biol Chem. 2013 Feb 15;288(7):5027-38
pubmed: 23269686
Cell Stem Cell. 2011 Dec 2;9(6):588-98
pubmed: 22136932
Cell. 2009 Jan 23;136(2):364-77
pubmed: 19167336
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):157-62
pubmed: 19109433
Stem Cells. 2013 Mar;31(3):458-66
pubmed: 23193063
Cell. 2009 Feb 6;136(3):411-9
pubmed: 19203577
Cell. 2012 Dec 21;151(7):1617-32
pubmed: 23260147
J Biol Chem. 2010 Jun 18;285(25):19483-90
pubmed: 20382743
Cell Stem Cell. 2018 Aug 02;23(2):266-275.e6
pubmed: 29910149
Stem Cell Reports. 2015 Dec 8;5(6):1155-1170
pubmed: 26651606
J Biol Chem. 2015 Feb 13;290(7):4500-11
pubmed: 25548277
Genes Dev. 2003 Aug 15;17(16):2048-59
pubmed: 12923055
Cell. 2006 Aug 25;126(4):663-76
pubmed: 16904174
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cell Res. 2014 Mar;24(3):293-306
pubmed: 24381111
Proc Natl Acad Sci U S A. 1982 Jul;79(13):4098-102
pubmed: 6955793
Cell Stem Cell. 2013 Apr 4;12(4):453-69
pubmed: 23499384
Sci Rep. 2016 Jan 14;6:19415
pubmed: 26762895
Nature. 2010 May 13;465(7295):175-81
pubmed: 20418860
Stem Cell Reports. 2013 Jul 11;1(2):183-97
pubmed: 24052952
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Biotechnol. 2008 Jan;26(1):101-6
pubmed: 18059259
Cell. 2014 Mar 13;156(6):1274-1285
pubmed: 24630727
Dev Cell. 2013 Jun 24;25(6):610-22
pubmed: 23747191
Wiley Interdiscip Rev Dev Biol. 2016 Jan-Feb;5(1):39-65
pubmed: 26383234
EMBO Rep. 2011 Apr;12(4):373-8
pubmed: 21399616
Genesis. 2010 Apr;48(4):220-32
pubmed: 20146354
Cell Rep. 2016 Feb 16;14(6):1540-1554
pubmed: 26832419
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Nat Immunol. 2013 Jul;14(7):714-22
pubmed: 23708251
Cell Res. 2015 Feb;25(2):169-80
pubmed: 25591928
Nat Commun. 2012;3:1279
pubmed: 23232409
Cell Rep. 2018 Jan 23;22(4):876-884
pubmed: 29420174
Cell Stem Cell. 2014 Sep 4;15(3):281-294
pubmed: 25192463
Cell Metab. 2019 Apr 2;29(4):979-992.e4
pubmed: 30527743
Cell. 1998 Oct 30;95(3):379-91
pubmed: 9814708
Cell. 1983 Apr;32(4):1105-13
pubmed: 6188535
Development. 2009 Feb;136(4):509-23
pubmed: 19168672
Trends Cell Biol. 2014 May;24(5):275-84
pubmed: 24370212
Cell. 2013 May 23;153(5):963-75
pubmed: 23706735
Nat Cell Biol. 2006 Oct;8(10):1114-23
pubmed: 16980957
Cell Stem Cell. 2010 Feb 5;6(2):167-74
pubmed: 20096661
Science. 2013 Aug 9;341(6146):651-4
pubmed: 23868920
Cell Stem Cell. 2008 Jun 5;2(6):525-8
pubmed: 18522845
Nature. 2015 Feb 19;518(7539):344-9
pubmed: 25693565
Nat Genet. 2006 Apr;38(4):431-40
pubmed: 16518401
Stem Cells. 2015 Mar;33(3):686-98
pubmed: 25331067
Stem Cells. 2011 Jun;29(6):964-71
pubmed: 21563278
Nat Cell Biol. 2007 Jun;9(6):625-35
pubmed: 17515932
Cell. 2008 Jun 13;133(6):1106-17
pubmed: 18555785
Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8257-E8266
pubmed: 27930301
Bioinformation. 2007 May 20;2(1):5-7
pubmed: 18084642
Nat Commun. 2019 Aug 2;10(1):3477
pubmed: 31375664
Nature. 2006 Nov 16;444(7117):364-8
pubmed: 17093407
Cell Stem Cell. 2014 Sep 4;15(3):295-309
pubmed: 25192464
Genomics Proteomics Bioinformatics. 2013 Oct;11(5):259-63
pubmed: 24095709
Nat Cell Biol. 2013 Sep;15(9):1089-97
pubmed: 23934214
Cell Stem Cell. 2008 Nov 6;3(5):543-54
pubmed: 18804426
Development. 2004 Aug;131(15):3805-19
pubmed: 15240551
Nat Genet. 2000 Apr;24(4):372-6
pubmed: 10742100
Cell. 2017 Jan 26;168(3):442-459.e20
pubmed: 28111071
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Nat Methods. 2010 Jan;7(1):56-9
pubmed: 20010831
Cell. 2009 Aug 21;138(4):722-37
pubmed: 19703398
Dev Cell. 2006 Oct;11(4):535-46
pubmed: 17011492
Nature. 2010 Mar 11;464(7286):306-10
pubmed: 20075857
Mol Ther. 2015 May;23(5):952-963
pubmed: 25666918
EMBO Rep. 2017 Feb;18(2):319-333
pubmed: 28007765
Nat Methods. 2011 May;8(5):409-12
pubmed: 21460823
Stem Cells. 2001;19(4):271-8
pubmed: 11463946
RNA. 2003 Apr;9(4):493-501
pubmed: 12649500
Epigenetics. 2010 Feb 16;5(2):149-58
pubmed: 20168089
Cell. 2015 Sep 24;163(1):230-45
pubmed: 26365490
Nat Biotechnol. 2015 Jul;33(7):761-8
pubmed: 26098450
Stem Cells. 2011 May;29(5):755-63
pubmed: 21305674
Cell Stem Cell. 2013 Sep 5;13(3):341-50
pubmed: 23871606
Nature. 2008 Jul 3;454(7200):49-55
pubmed: 18509334
Development. 1990 Nov;110(3):815-21
pubmed: 2088722
EMBO Rep. 2011 Jul 01;12(7):720-6
pubmed: 21617704
EMBO J. 2017 Jan 4;36(1):61-78
pubmed: 27908934