TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons

J. Cell. Mol. Med., 2014 · DOI: 10.1111/jcmm.12298 · Published: July 1, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

The study investigates the role of TGF-β signaling in neural stem cells. It explores how TGF-β influences stem cell quiescence and the generation of new neurons in the adult brain. The research uses transgenic mice to express TGF-β1 and analyzes its effects on cell proliferation, quiescence, neuronal survival, and differentiation. Gene expression profiling identifies targets of TGF-β1 signaling. Results indicate that TGF-β1 promotes stem cell quiescence while also supporting neuronal survival. This suggests TGF-β1 could be a target for interventions in aging and neurodegenerative diseases.

Study Duration

54 days

Participants

Transgenic mice (N = 4 and TGF-b1-off mice; N = 4)

Evidence Level

Not specified

Key Findings

1
TGF-b1 signalling in the adult neurogenic niche contributes to stem cell quiescence, and to neuronal differentiation, maturation and survival of newly generated cells.
2
Prolonged expression of TGF-b1 signalling was associated with a reduced SGZ cell proliferation, but with an enhanced survival of newly generated neurons.
3
TGF-b1 stimulation induced neuronal functionality, i.e. the capacity of NPCs to generate action potentials, and promoted NPCs’ survival.

Research Summary

This study investigates the role of TGF-β1 signaling in the adult neurogenic niche, focusing on its impact on neural stem cell quiescence and neuronal differentiation. The research demonstrates that TGF-β1 promotes stem cell quiescence while simultaneously enhancing the survival of newly generated neurons. Gene expression analysis reveals that TGF-β1 influences genes associated with cell cycle regulation, stem cell maintenance, and neuronal differentiation, suggesting its potential as a therapeutic target for neurodegenerative conditions.

Practical Implications

Therapeutic Target

TGF-β1 signaling pathway may be a potential therapeutic target for interventions in aging and neurodegenerative diseases.

Understanding Brain Homeostasis

The healthy brain has a sustained expression of TGF-b1 that might be required for a proper brain homeostasis.

Stimulating Neurogenesis

Inhibiting TGF-b signalling might unlock NPCs from a TGF-b-induced cell cycle arrest.

Study Limitations

1
The molecular and cellular circumstances under which TGF-b1 promotes either the one or the other require further investigation
2
Further experiments are needed to sort out the different effects of activins and of TGF-b1 on TGF signalling in NPCs and the differential contribution of these cytokines to neurogenesis.
3
Functional ion channel expression was not analysed in full detail in this study

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