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In Vivo Direct Reprogramming of Resident Glial Cells into Interneurons by Intracerebral Injection of Viral Vectors
Published on: June 17, 2019
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Transient CREB-mediated transcription is key in direct neuronal reprogramming
Sergio Gascón1, Felipe Ortega2, Magdalena Götz3
1Ludwig-Maximilians University of Munich, Physiological Genomics, Biomedical Center (BMC), Planegg-Martinsried, Germany; Institute for Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany.
Neurogenesis (Austin, Tex.)
|March 22, 2017
Summary
Transiently activating CREB enhances neuronal reprogramming of astrocytes. Persistent activation or inhibition of CREB, however, hinders this process, with inhibition increasing cell death.
Area of Science:
- Cellular reprogramming
- Neuroscience
- Molecular biology
Background:
- Small molecules like Forskolin (Fk) and neuronal determinants can induce cell conversion into neurons.
- Forskolin activates cAMP-dependent pathways, including CREB (cAMP response element-binding protein) activity.
Purpose of the Study:
- To investigate the specific role and temporal dynamics of CREB in neuronal reprogramming.
- To understand how modulating CREB activity impacts astrocyte-to-neuron conversion.
Main Methods:
- Utilized a dominant-positive CREB (CREB-VP16) for activation and a dominant-negative form (ICER) for inactivation.
- Investigated the effect of transient versus persistent CREB modulation during Ascl1-mediated astrocyte reprogramming.
- Assessed neuronal conversion efficiency and cell viability.
Main Results:
- Transient expression and subsequent inactivation of CREB-VP16 significantly improved astrocyte-to-neuron conversion mediated by Ascl1.
- Sustained activation by CREB-VP16 or persistent inhibition by ICER impaired neuronal reprogramming.
- Prolonged ICER expression led to increased cell death during the reprogramming process.
Conclusions:
- Transient activation of CREB is a critical factor for efficient neuronal reprogramming.
- The temporal control of CREB activity is essential for successful cell fate conversion into neurons.
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