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Identification of Jmjd1a as a STAT3 downstream gene in mES cells

Song Yi Ko1, Hye Yoon Kang, Hyun Sil Lee

  • 1School of Biological Sciences, and Institute of Molecular Biology and Genetics, Seoul National University.

Cell Structure and Function
|September 22, 2006
PubMed

Insights

Leukemia inhibitory factor (LIF) maintains mouse embryonic stem cell pluripotency via STAT3 activation. Researchers identified Jmjd1a as a key downstream target gene essential for this process.

Area of Science:

  • Stem Cell Biology
  • Molecular Signaling
  • Gene Regulation

Background:

  • Mouse embryonic stem (mES) cells require leukemia inhibitory factor (LIF) for maintaining pluripotency.
  • Signal transducer and activator of transcription 3 (STAT3) activation is crucial for LIF-mediated pluripotency maintenance.
  • The specific downstream pathways regulated by STAT3 in this context remain largely uncharacterized.

Purpose of the Study:

  • To identify STAT3-regulated downstream target genes involved in LIF-dependent pluripotency maintenance in mES cells.
  • To investigate the role of identified target genes in the pluripotency network.

Main Methods:

  • Differential display reverse transcription PCR (DD-RT PCR) was employed to compare gene expression in the presence and absence of LIF.
  • Candidate gene validation and expression analysis were performed.
  • Chromatin immunoprecipitation or DNA-binding assays were used to assess STAT3 binding to target gene promoters.

Main Results:

  • Eight genes were identified with expression levels significantly dependent on LIF.
  • Jmjd1a expression was found to be downregulated upon LIF withdrawal, decreasing by day 1 and disappearing by day 3.
  • STAT3 was demonstrated to bind to the promoter region of the Jmjd1a gene.

Conclusions:

  • Jmjd1a is a novel downstream target of STAT3 signaling in LIF-dependent mES cell pluripotency.
  • Jmjd1a may play a critical role as a signaling molecule in maintaining the undifferentiated state of mES cells.

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