Neural stem cells: developmental mechanisms and disease modeling

Cell Tissue Res, 2018 · DOI: 10.1007/s00441-017-2738-1 · Published: January 1, 2018

Regenerative Medicine Neurology Research Methodology & Design

Simple Explanation

Neural stem cells (NSCs) are the stem cells of the nervous system. During development they give rise to the entire nervous system. In adults, a small number of NSCs remain and are mostly quiescent; however, ample evidence supports their important roles in plasticity, aging, disease, and regeneration of the nervous system. The behavior and fate of stem cells are strongly influenced by their specific anatomical locations and surrounding cell types, called “ the stem cell niche.” The niche provides physical support to host or anchor stem cells, and supplies factors to maintain and regulate them. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs) and induced PSCs (iPSCs), offer a model system to reveal cellular and molecular events underlying normal and abnormal neural development in humans.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
During development, the central nervous system (CNS) is generated from a small number of neural stem cells (NSCs) lining the neural tube.
2
In adult brains, NSCs are reduced and become restricted to specific brain regions. In rodents, both NSCs and ongoing neurogenesis have been widely documented in the SVZ of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus
3
One of the strongest negative regulators of adult neurogenesis is aging. Both intrinsic and extrinsic components regulate the limitations of NSC proliferation and function

Research Summary

Neural stem cells (NSCs) are the stem cells of the nervous system. During development they give rise to the entire nervous system. Because NSCs are regulated by both intrinsic genetic and epigenetic programs and extrinsic stimuli transduced through the stem cell niche, dysregulation of NSCs due to either genetic causes or environmental impacts may lead to disease. The advancement in iPSC and gene editing technology has transformed the field of human disease modeling.

Practical Implications

Therapeutic Strategies

NSCs have been a focal point for cell-based therapeutic strategies in the brain and spinal cord.

Disease Modeling

Understanding NSC regulation gives us the opportunity to explore mechanisms of development, as well as disorders resulting from their dysfunction.

Drug Development

Using patient-derived neurons to study monogenic epilepsy-in-a-dish can translate findings to human therapeutics.

Study Limitations

1
Limited number of NSCs residing in the tissue.
2
Challenges remain regarding cell lineage control, in vivo NSC behavior, three dimensional cellular interactions, and preservation of epigenetic and aging marks.
3
Lineage control in neural differentiation from pluripotent stem cells is a major hurdle.

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