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Novel spliced variants of OCT4, OCT4C and OCT4C1, with distinct expression patterns and functions in pluripotent and

Mahshid Malakootian1, Fatemeh Mirzadeh Azad2, Parisa Naeli2

  • 1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

European Journal of Cell Biology
|May 7, 2017
PubMed

Insights

Two novel OCT4 variants, OCT4C and OCT4C1, were discovered, originating from a new exon (E0) and highly expressed in stem cells. Their expression decreased during neural differentiation, revealing complex OCT4 gene regulation.

Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Gene Regulation

Background:

  • OCT4 is a key regulator of pluripotency with known spliced variants and pseudogenes.
  • Understanding OCT4's full repertoire is crucial for stem cell research and cancer biology.

Purpose of the Study:

  • To identify and characterize novel spliced variants of the OCT4 gene.
  • To investigate the expression patterns and regulatory relationships of these variants in stem cells and during differentiation.
  • To explore the interplay between OCT4 and the long non-coding RNA PSORS1C3.

Main Methods:

  • Identification of novel OCT4 spliced variants (OCT4C, OCT4C1) utilizing a novel upstream exon (E0).
  • Analysis of OCT4C/C1 expression in embryonic stem (ES) and induced pluripotent stem (iPS) cells and during neural differentiation.
  • Investigated the structure and variants of the co-localized lncRNA PSORS1C3.
  • Performed knock-down experiments for OCT4C/C1 in stem cell lines to assess effects on OCT4A, OCT4B, OCT4B1, and PSORS1C3 expression.

Main Results:

  • Discovery of OCT4C and OCT4C1, variants lacking Exon1 but starting from a novel exon (E0).
  • OCT4C/C1 show high expression in ES and iPS cells, sharply decreasing upon neural differentiation induction.
  • The lncRNA PSORS1C3 shares intertwined exons with OCT4, including a novel exon (E0) upstream of OCT4's E0.
  • OCT4C/C1 knockdown led to downregulation of PSORS1C3 and OCT4A, and upregulation of OCT4B and OCT4B1.

Conclusions:

  • The study reveals two new OCT4 spliced variants, OCT4C and OCT4C1, expanding the known OCT4 gene structure.
  • These variants are dynamically regulated during stem cell differentiation, suggesting roles in maintaining pluripotency.
  • The complex genomic organization and regulatory interactions between OCT4 and PSORS1C3 highlight novel aspects of gene expression control in stem and tumor cells.
Keywords:
DifferentiationOCT4COCT4C1PSORS1C3Stem celllncRNA

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