TAZ Represses the Neuronal Commitment of Neural Stem Cells.
Natalia Robledinos-AntónMaribel EscollKun-Liang GuanAntonio CuadradoPublished in: Cells (2020)
The mechanisms involved in regulation of quiescence, proliferation, and reprogramming of Neural Stem Progenitor Cells (NSPCs) of the mammalian brain are still poorly defined. Here, we studied the role of the transcriptional co-factor TAZ, regulated by the WNT and Hippo pathways, in the homeostasis of NSPCs. We found that, in the murine neurogenic niches of the striatal subventricular zone and the dentate gyrus granular zone, TAZ is highly expressed in NSPCs and declines with ageing. Moreover, TAZ expression is lost in immature neurons of both neurogenic regions. To characterize mechanistically the role of TAZ in neuronal differentiation, we used the midbrain-derived NSPC line ReNcell VM to replicate in a non-animal model the factors influencing NSPC differentiation to the neuronal lineage. TAZ knock-down and forced expression in NSPCs led to increased and reduced neuronal differentiation, respectively. TEADs-knockdown indicated that these TAZ co-partners are required for the suppression of NSPCs commitment to neuronal differentiation. Genetic manipulation of the TAZ/TEAD system showed its participation in transcriptional repression of SOX2 and the proneuronal genes ASCL1, NEUROG2, and NEUROD1, leading to impediment of neurogenesis. TAZ is usually considered a transcriptional co-activator promoting stem cell proliferation, but our study indicates an additional function as a repressor of neuronal differentiation.
Keyphrases
- cerebral ischemia
- cell proliferation
- transcription factor
- neural stem cells
- spinal cord injury
- poor prognosis
- gene expression
- stem cells
- genome wide
- signaling pathway
- subarachnoid hemorrhage
- dna methylation
- long non coding rna
- parkinson disease
- hepatitis c virus
- white matter
- inflammatory response
- binding protein
- men who have sex with men
- hiv testing
- nuclear factor
- antiretroviral therapy
- hiv infected
- heat shock protein
- deep brain stimulation