T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications

被引：48

作者：

Lluis, Frederic ^{[1
]}

Ombrato, Luigi ^{[1
]}

Pedone, Elisa ^{[1
]}

Pepe, Stefano ^{[1
]}

Merrill, Bradley J. ^{[2
]}

Pia Cosma, Maria ^{[1
,3
,4
]}

机构：

[1] Univ Pompeu Fabra, Ctr Regulacio Genom, Barcelona 08003, Spain

[2] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA

[3] Inst Catalana Recerca & Estudis Avancats, Barcelona 08003, Spain

[4] CNR, Inst Genet & Biophys, I-80134 Naples, Italy

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 29期

基金：

欧洲研究理事会;

关键词：

Wnt pathway; induced pluripotent stem cell generation; PLURIPOTENT STEM-CELLS; SELF-RENEWAL; EXOGENOUS SOX2; ACTIVATION; CIRCUITRY; ABSENCE; FUSION; CORE;

D O I：

10.1073/pnas.1017402108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of beta-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3(-/-) ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.

引用

页码：11912 / 11917

页数：6

共 28 条

[1] Reprogramming towards pluripotency requires AID-dependent DNA demethylation [J].

Bhutani, Nidhi ;

Brady, Jennifer J. ;

Damian, Mara ;

Sacco, Alessandra ;

Corbel, Stephane Y. ;

Blau, Helen M. .

NATURE, 2010, 463 (7284) :1042-U57

[2] Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells [J].

Cole, Megan F. ;

Johnstone, Sarah E. ;

Newman, Jamie J. ;

Kagey, Michael H. ;

Young, Richard A. .

GENES & DEVELOPMENT, 2008, 22 (06) :746-755

[3] Niche-independent symmetrical self-renewal of a mammalian tissue stem cell [J].

Conti, L ;

Pollard, SM ;

Gorba, T ;

Reitano, E ;

Toselli, M ;

Biella, G ;

Sun, YR ;

Sanzone, S ;

Ying, QL ;

Cattaneo, E ;

Smith, A .

PLOS BIOLOGY, 2005, 3 (09) :1594-1606

[4] Nuclei of embryonic stem cells reprogram somatic cells [J].

Do, JT ;

Schöler, HR .

STEM CELLS, 2004, 22 (06) :941-949

[5] Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression [J].

Eminli, Sarah ;

Utikal, Jochen ;

Arnold, Katrin ;

Jaenisch, Rudolf ;

Hochedlinger, Konrad .

STEM CELLS, 2008, 26 (10) :2467-2474

[6] Phosphorylation of TCF Proteins by Homeodomain-interacting Protein Kinase 2 [J].

Hikasa, Hiroki ;

Sokol, Sergei Y. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (14) :12093-12100

[7] Regulation of TCF3 by Wnt-Dependent Phosphorylation during Vertebrate Axis Specification [J].

Hikasa, Hiroki ;

Ezan, Jerome ;

Itoh, Keiji ;

Li, Xiaotong ;

Klymkowsky, Michael W. ;

Sokol, Sergei Y. .

DEVELOPMENTAL CELL, 2010, 19 (04) :521-532

[8] Epigenetic reprogramming and induced pluripotency [J].

Hochedlinger, Konrad ;

Plath, Kathrin .

DEVELOPMENT, 2009, 136 (04) :509-523

[9] Wnt signalling: variety at the core [J].

Hoppler, Stefan ;

Kavanagh, Claire Louise .

JOURNAL OF CELL SCIENCE, 2007, 120 (03) :385-393

[10] Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming [J].

Jaenisch, Rudolf ;

Young, Richard .

CELL, 2008, 132 (04) :567-582

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