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Novel crosstalk between Vps26a and Nox4 signaling during neurogenesis

Seon-A Choi1,2,3, Young-Hyun Kim2,4, Young-Ho Park1,2,4

  • 1Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do, 28116, Republic of Korea.

Cell Death and Differentiation
|November 23, 2018
PubMed

Insights

The retromer complex component Vps26a regulates embryonic stem cell (ESC) stemness during neurogenesis by interacting with Nox4, reactive oxygen species (ROS), and ERK1/2 signaling.

Area of Science:

  • Cell Biology
  • Stem Cell Biology
  • Molecular Neuroscience

Background:

  • Embryonic stem cells (ESCs) possess the ability to self-renew and differentiate.
  • The molecular mechanisms governing stemness maintenance and differentiation are complex and not fully understood.
  • The role of the retromer complex in stem cell differentiation remains largely unexplored.

Purpose of the Study:

  • To investigate the involvement of the retromer complex, specifically Vps26a, in regulating stemness and neurogenesis in ESCs.
  • To elucidate the molecular pathways linking Vps26a to stemness maintenance and differentiation.
  • To explore the potential therapeutic applications of these findings in ESC-based strategies.

Main Methods:

  • Utilized Vps26a-deficient (Vps26a-/-) and knockdown ESCs and embryonic carcinoma cells.
  • Assessed stemness and neuronal differentiation markers.
  • Measured reactive oxygen species (ROS) levels and employed antioxidants and NADPH oxidase (Nox) inhibitors.
  • Investigated interactions between Vps26a, Nox4, and ERK1/2 signaling pathways.

Main Results:

  • Vps26a deficiency or knockdown suppressed stemness loss and neurogenesis in ESCs.
  • Vps26a-/- ESCs exhibited lower ROS levels during differentiation.
  • Antioxidant or Nox inhibition restored stemness in wild-type cells.
  • Vps26a interacts with Nox4, influencing ROS levels and ERK1/2 activation, demonstrating a mutual dependency.

Conclusions:

  • Vps26a plays a crucial role in regulating ESC stemness during neurogenesis.
  • Vps26a cooperates with the Nox4/ROS/ERK1/2 signaling cascade to control stemness.
  • Findings highlight the crosstalk between retromer function and redox signaling in stem cell regulation.
  • This research may inform the development of ESC-based therapies for cell production.

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