REST and RCOR genes display distinct expression profiles in neurons and astrocytes using 2D and 3D human pluripotent stem cell models
Simon Maksour,
Neville Ng,
Amy J. Hulme,
Sara Miellet,
Martin Engel,
Sonia Sanz Muñoz,
Rachelle Balez,
Ben Rollo,
Rocio K. Finol-Urdaneta,
Lezanne Ooi,
Mirella Dottori
Affiliations
Simon Maksour
School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Neville Ng
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Amy J. Hulme
School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
Sara Miellet
School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
Martin Engel
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Sonia Sanz Muñoz
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Rachelle Balez
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Ben Rollo
Department of Neuroscience, Monash University, Melbourne, VIC, Australia
Rocio K. Finol-Urdaneta
School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
Lezanne Ooi
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia
Mirella Dottori
School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia; Corresponding author. School of Medical and Indigenous Health Sciences, University of Wollongong, NSW, Australia.
Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor involved in neurodevelopment and neuroprotection. REST forms a complex with the REST corepressors, CoREST1, CoREST2, or CoREST3 (encoded by RCOR1, RCOR2, and RCOR3, respectively). Emerging evidence suggests that the CoREST family can target unique genes independently of REST, in various neural and glial cell types during different developmental stages. However, there is limited knowledge regarding the expression and function of the CoREST family in human neurodevelopment. To address this gap, we employed 2D and 3D human pluripotent stem cell (hPSC) models to investigate REST and RCOR gene expression levels. Our study revealed a significant increase in RCOR3 expression in glutamatergic cortical and GABAergic ventral forebrain neurons, as well as mature functional NGN2-induced neurons. Additionally, a simplified astrocyte transdifferentiation protocol resulted in a significant decrease in RCOR2 expression following differentiation. REST expression was notably reduced in mature neurons and cerebral organoids. In summary, our findings provide the first insights into the cell-type-specific expression patterns of RCOR genes in human neuronal and glial differentiation. Specifically, RCOR3 expression increases in neurons, while RCOR2 levels decrease in astrocytes. The dynamic expression patterns of REST and RCOR genes during hPSC neuronal and glial differentiation underscore the potential distinct roles played by REST and CoREST proteins in regulating the development of these cell types in humans.
