The Transcriptional Foundation of Pluripotency

Overview

Journal Development

Specialty Biology

Date 2009 Jun 23

PMID 19542351

Citations 208

Authors

Ian Chambers

Simon R Tomlinson

Affiliations

Soon will be listed here.

Abstract

A fundamental goal in biology is to understand the molecular basis of cell identity. Pluripotent embryonic stem (ES) cell identity is governed by a set of transcription factors centred on the triumvirate of Oct4, Sox2 and Nanog. These proteins often bind to closely localised genomic sites. Recent studies have identified additional transcriptional modulators that bind to chromatin near sites occupied by Oct4, Sox2 and Nanog. This suggests that the combinatorial control of gene transcription might be fundamental to the ES cell state. Here we discuss how these observations advance our understanding of the transcription factor network that controls pluripotent identity and highlight unresolved issues that arise from these studies.

Citing Articles

Optimizing Cardiomyocyte Differentiation: Comparative Analysis of Bone Marrow and Adipose-Derived Mesenchymal Stem Cells in Rats Using 5-Azacytidine and Low-Dose FGF and IGF Treatment.

Farag A, Ngeun S, Kaneda M, Aboubakr M, Tanaka R Biomedicines. 2024; 12(8).

PMID: 39200387 PMC: 11352160. DOI: 10.3390/biomedicines12081923.

Novel cell states arise in embryonic cells devoid of key reprogramming factors.

Youlten S, Miao L, Hoppe C, Boswell C, Musaev D, Abdelmessih M bioRxiv. 2024; .

PMID: 38798464 PMC: 11118305. DOI: 10.1101/2024.05.13.593729.

Txnip regulates the Oct4-mediated pluripotency circuitry via metabolic changes upon differentiation.

Kwak S, Song C, Cho Y, Choi I, Byun J, Jung H Cell Mol Life Sci. 2024; 81(1):142.

PMID: 38485770 PMC: 10940461. DOI: 10.1007/s00018-024-05161-y.

Novel Approaches to Studying SLC13A5 Disease.

Beltran A Metabolites. 2024; 14(2).

PMID: 38392976 PMC: 10890222. DOI: 10.3390/metabo14020084.

Myogenic Differentiation and Immunomodulatory Properties of Rat Adipose-Derived Mesenchymal Stem/Stromal Cells.

Ngeun S, Shimizu M, Kaneda M Biology (Basel). 2024; 13(2).

PMID: 38392291 PMC: 10886144. DOI: 10.3390/biology13020072.

References

Ambrosetti D, Basilico C, Dailey L . Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol Cell Biol. 1997; 17(11):6321-9. PMC: 232483. DOI: 10.1128/MCB.17.11.6321. View

Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S . Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007; 448(7150):191-5. DOI: 10.1038/nature05950. View

Xu J, Pope S, Jazirehi A, Attema J, Papathanasiou P, Watts J . Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Proc Natl Acad Sci U S A. 2007; 104(30):12377-82. PMC: 1941477. DOI: 10.1073/pnas.0704579104. View

Kim J, Chu J, Shen X, Wang J, Orkin S . An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 2008; 132(6):1049-61. PMC: 3837340. DOI: 10.1016/j.cell.2008.02.039. View

Ema M, Mori D, Niwa H, Hasegawa Y, Yamanaka Y, Hitoshi S . Krüppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs. Cell Stem Cell. 2008; 3(5):555-67. DOI: 10.1016/j.stem.2008.09.003. View

Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen H, John R . Chromatin signatures of pluripotent cell lines. Nat Cell Biol. 2006; 8(5):532-8. DOI: 10.1038/ncb1403. View

Tesar P, Chenoweth J, Brook F, Davies T, Evans E, Mack D . New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. 2007; 448(7150):196-9. DOI: 10.1038/nature05972. View

Liang J, Wan M, Zhang Y, Gu P, Xin H, Jung S . Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol. 2008; 10(6):731-9. DOI: 10.1038/ncb1736. View

Falkner F, Zachau H . Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984; 310(5972):71-4. DOI: 10.1038/310071a0. View

10.

Cole M, Johnstone S, Newman J, Kagey M, Young R . Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells. Genes Dev. 2008; 22(6):746-55. PMC: 2275428. DOI: 10.1101/gad.1642408. View

11.

Jaenisch R, Young R . Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 2008; 132(4):567-82. PMC: 4142810. DOI: 10.1016/j.cell.2008.01.015. View

12.

Sridharan R, Tchieu J, Mason M, Yachechko R, Kuoy E, Horvath S . Role of the murine reprogramming factors in the induction of pluripotency. Cell. 2009; 136(2):364-77. PMC: 3273494. DOI: 10.1016/j.cell.2009.01.001. View

13.

Jiang J, Chan Y, Loh Y, Cai J, Tong G, Lim C . A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol. 2008; 10(3):353-60. DOI: 10.1038/ncb1698. View

14.

Williams Jr D, Cai M, Clore G . Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. J Biol Chem. 2003; 279(2):1449-57. DOI: 10.1074/jbc.M309790200. View

15.

Mackay J, Sunde M, Lowry J, Crossley M, Matthews J . Protein interactions: is seeing believing?. Trends Biochem Sci. 2007; 32(12):530-1. DOI: 10.1016/j.tibs.2007.09.006. View

16.

Navarro P, Avner P . When X-inactivation meets pluripotency: an intimate rendezvous. FEBS Lett. 2009; 583(11):1721-7. DOI: 10.1016/j.febslet.2009.03.043. View

17.

Remenyi A, Lins K, Nissen L, Reinbold R, Scholer H, Wilmanns M . Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev. 2003; 17(16):2048-59. PMC: 196258. DOI: 10.1101/gad.269303. View

18.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

19.

Boyer L, Lee T, Cole M, Johnstone S, Levine S, Zucker J . Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122(6):947-56. PMC: 3006442. DOI: 10.1016/j.cell.2005.08.020. View

20.

Niwa H, Toyooka Y, Shimosato D, Strumpf D, Takahashi K, Yagi R . Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell. 2005; 123(5):917-29. DOI: 10.1016/j.cell.2005.08.040. View