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

Jian-Chien Dominic Heng1, Bo Feng, Jianyong Han

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

Cell Stem Cell
|January 26, 2010
PubMed

Insights

Researchers discovered that Nr5a2 can replace Oct4 for induced pluripotent stem cell (iPSC) generation. This finding reveals a new Oct4-free reprogramming code, enhancing stem cell research possibilities.

Area of Science:

  • Stem cell biology
  • Epigenetics and gene regulation
  • Molecular biology

Background:

  • Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) using specific transcription factors, notably Oct4, Sox2, Klf4, and c-Myc.
  • Oct4 is considered essential for pluripotency induction, with no known substitute, while other factors can be replaced.

Purpose of the Study:

  • To investigate if alternative transcription factors can substitute for Oct4 in the reprogramming process.
  • To explore the potential of the orphan nuclear receptor Nr5a2 (Lrh-1) in iPSC derivation.
  • To understand the molecular mechanisms underlying Oct4-independent reprogramming.

Main Methods:

  • Introduction of transcription factors, including Nr5a2, into mouse somatic cells to induce pluripotency.
  • Utilizing sumoylation mutants of Nr5a2 with enhanced transcriptional activity.
  • Genome-wide location analysis to identify gene targets of Nr5a2, Sox2, and Klf4.
  • Assessing the activation of Nanog by Nr5a2.

Main Results:

  • The orphan nuclear receptor Nr5a2 successfully replaced Oct4 in deriving iPSCs from mouse somatic cells.
  • Nr5a2 enhanced reprogramming efficiency, with sumoylation mutants further increasing this efficiency.
  • Genome-wide analysis showed shared gene targets between Nr5a2, Sox2, and Klf4, indicating cooperative action.
  • Nr5a2 was found to activate Nanog, contributing to the reprogramming process.

Conclusions:

  • Unrelated transcription factors, specifically Nr5a2, can substitute for Oct4 in iPSC generation.
  • This study uncovers an exogenous Oct4-free reprogramming code, expanding the toolkit for stem cell reprogramming.
  • The findings highlight the collaborative roles of transcription factors like Nr5a2, Sox2, and Klf4 in mediating pluripotency.

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