Transcriptional Control of Embryonic and Induced Pluripotent Stem Cells

Abstract

Embryonic stem cells (ESCs) have the potential to generate virtually any cell type or tissue type in the body. This remarkable plasticity has yielded great interest in using these cells to understand early development and in treating human disease. In an effort to understand the basis of ESC pluripotency, genetic and genomic studies have revealed transcriptional regulatory circuitry that maintains the pluripotent cell state and poises the genome for downstream activation. Critical components of this circuitry include ESC transcription factors, chromatin regulators, histone modifications, signaling molecules and regulatory RNAs. This article will focus on our current understanding of these components and how they influence ESC and induced pluripotent stem cell states. Emerging themes include regulation of the pluripotent genome by a core set of transcription factors, transcriptional poising of developmental genes by chromatin regulatory complexes and the establishment of multiple layers of repression at key genomic loci.

KEYWORDS::

• chromatin
• embryonic stem cells
• epigenetic
• ESC
• histone modification
• induced pluripotent stem cell
• iPSC
• Oct4
• pluripotency
• reprogramming
• Sox2
• transcription

Acknowledgements

The author would like to thank Rick Young, Rudolf Jaenisch, Tony Lee, Pete Rahl, Steve Bilodeau, Mike Kagey, Lee Lawton, Alan Mullen, Frank Soldner, Alex Marson, Garrett Frampton, Laurie Boyer, Stuart Levine and Evaline Steine for critical reading of the manuscript and helpful discussions, as well as Tom Dicesare for graphic support.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.