The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells

Jian-Chien Dominic Heng; Bo Feng; Jianyong Han; Jianming Jiang; Petra Kraus; Jia-Hui Ng; Yuriy L Orlov; Mikael Huss; Lin Yang; Thomas Lufkin; Bing Lim; Huck-Hui Ng

doi:10.1016/j.stem.2009.12.009

The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells

Cell Stem Cell. 2010 Feb 5;6(2):167-74. doi: 10.1016/j.stem.2009.12.009. Epub 2010 Jan 21.

Authors

Jian-Chien Dominic Heng¹, Bo Feng, Jianyong Han, Jianming Jiang, Petra Kraus, Jia-Hui Ng, Yuriy L Orlov, Mikael Huss, Lin Yang, Thomas Lufkin, Bing Lim, Huck-Hui Ng

Affiliation

¹ Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore.

PMID: 20096661
DOI: 10.1016/j.stem.2009.12.009

Abstract

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) with the introduction of Oct4, Sox2, Klf4, and c-Myc. Among these four factors, Oct4 is critical in inducing pluripotency because no transcription factor can substitute for Oct4, whereas Sox2, Klf4, and c-Myc can be replaced by other factors. Here we show that the orphan nuclear receptor Nr5a2 (also known as Lrh-1) can replace Oct4 in the derivation of iPSCs from mouse somatic cells, and it can also enhance reprogramming efficiency. Sumoylation mutants of Nr5a2 with enhanced transcriptional activity can further increase reprogramming efficiency. Genome-wide location analysis reveals that Nr5a2 shares many common gene targets with Sox2 and Klf4, which suggests that the transcription factor trio works in concert to mediate reprogramming. We also show that Nr5a2 works in part through activating Nanog. Together, we show that unrelated transcription factors can replace Oct4 and uncovers an exogenous Oct4-free reprogramming code.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cells, Cultured
Cellular Reprogramming*
Epigenesis, Genetic
Gene Expression Profiling
Genome-Wide Association Study
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Mutation
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism*
Protein Binding
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism
SUMO-1 Protein / metabolism
Steroidogenic Factor 1 / genetics
Steroidogenic Factor 1 / metabolism

Substances

KLF4 protein, human
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Nr5a2 protein, mouse
Octamer Transcription Factor-3
Pou5f1 protein, mouse
Receptors, Cytoplasmic and Nuclear
SOXB1 Transcription Factors
SUMO-1 Protein
Sox2 protein, mouse
Steroidogenic Factor 1
steroidogenic factor 1, mouse