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Differentiation and Characterization of Neural Progenitors and Neurons from Mouse Embryonic Stem Cells
Published on: May 15, 2020
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Mitochondrial Complex I Function Is Essential for Neural Stem/Progenitor Cells Proliferation and Differentiation.
Daniel Cabello-Rivera1,2,3, Helia Sarmiento-Soto1,2, José López-Barneo1,2,3
1Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain.
Frontiers in Neuroscience
|July 13, 2019
Summary
Mitochondrial complex I (MCI) dysfunction impairs neural stem cell proliferation and differentiation, crucial for brain development. This dysfunction leads to severe developmental defects and early death in knockout mice.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Metabolism
Background:
- Neurogenesis relies on neural stem cell (NSC) activity.
- Mitochondrial metabolism influences NSC homeostasis and differentiation.
- The specific role of mitochondrial function in neurogenesis needs further study.
Purpose of the Study:
- To investigate the impact of mitochondrial complex I (MCI) dysfunction on NSC viability, proliferation, and differentiation.
- To analyze the effects on neural progeny survival.
- To understand the necessity of functional MCI in neurogenesis.
Main Methods:
- Generated a conditional knockout mouse model (hGFAP-NDUFS2) with suppressed NDUFS2 protein expression in radial glial cells (RGCs) and NSCs.
- Conducted in vitro studies on subventricular zone NSCs.
- Analyzed perinatal brain development and survival rates.
Main Results:
- MCI dysfunction did not severely affect central NSC survival but inhibited perinatal brain development.
- Ndufs2 knockout mice died before postnatal day 10.
- In vitro studies revealed that functional MCI is required for NSC ATP production, proliferation, and differentiation into neurons and oligodendrocytes.
Conclusions:
- A functional MCI and proper oxidative phosphorylation are essential for NSC proliferation and differentiation.
- MCI dysfunction profoundly impacts glia-like NSC proliferation, differentiation, and maturation of neural progeny.
- These findings highlight the critical role of mitochondrial function in mammalian brain development and neurogenesis.
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