OCT4, SOX2 and NANOG co-regulate glycolysis and participate in somatic induced reprogramming

Ying Ding1,2, Xia Yuan1,2, Yichen Zou1,2

  • 1Key Laboratory of Animal Genetics, Breeding and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009 China.

Cytotechnology
|June 23, 2022
PubMed

Insights

OCT4, SOX2, and NANOG (OSN) transcription factors coordinate glycolysis regulation during somatic cell reprogramming into induced pluripotent stem cells (iPSCs). This study reveals OSN

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Metabolic Regulation

Background:

  • OCT4, SOX2, and NANOG (OSN) are crucial for maintaining stem cell pluripotency.
  • Glycolysis is increasingly recognized for its role in somatic cell reprogramming.
  • The synergistic effects of OSN factors on glycolysis during reprogramming remain underexplored.

Purpose of the Study:

  • To investigate the coordinated regulation of glycolysis by OSN factors during induced pluripotent stem cell (iPSC) generation.
  • To elucidate the role of glycolysis in the reprogramming of chicken embryonic fibroblasts (CEFs) into iPSCs.

Main Methods:

  • Reprogramming of CEFs into iPSCs using OCT4, SOX2, NANOG, and LIN28.
  • RNA sequencing (RNA-seq) to analyze gene expression profiles.
  • Measurement of glycolysis gene expression, glucose uptake, and lactate production.
  • Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) to assess transcription factor enrichment.

Main Results:

  • Chicken iPSCs exhibited high expression of pluripotency genes and key glycolysis genes (Hk1, Pfkp, Ldha) compared to CEFs.
  • iPSCs demonstrated significantly higher glycolysis levels, including glucose uptake and lactate production, than CEFs.
  • ChIP-qPCR confirmed enrichment of SOX2 and NANOG at the promoter regions of glycolysis genes Hk1, Pfkp, and Ldha, but not OCT4.

Conclusions:

  • OCT4, SOX2, and NANOG collectively regulate glycolysis during somatic cell reprogramming.
  • Enhanced glycolysis is a characteristic feature of chicken iPSCs.
  • These findings provide a foundation for understanding the molecular mechanisms of somatic cell reprogramming.

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