EXPRESSION SIGNATURE ASSOCIATED WITH CORTICAL MATURATION AND ITS POTENTIAL ASSOCIATION WITH GENETIC RISK FOR SCHIZOPHRENIA

Autor: Greg W Anderson, Sang Lee, Gerome Breen, Deepak Srivastava, Douglas F. Nixon, Robin M. Murray, Timothy R. Powell, Rodrigo R.R. Duarte, Nicholas John Bray
Rok vydání: 2019
Předmět:
Zdroj: European Neuropsychopharmacology. 29:S987-S988
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2017.08.367
Popis: Background The human neural progenitor cell line CTX0E16 is a robust source of forebrain-like glutamatergic cortical neurons that display intrinsic functional properties (Anderson et al., 2015, Stem Cell Res). This cell line was obtained from the embryonic cortex of a 12-week gestation XY fetus, and conditionally immortalised by ectopic expression of the c-MycER TAM transgene. This construct allows the stem cells to be maintained in a proliferative state under the presence of hydroxytamoxifen (4-OHT), while removal of 4-OHT and growth factors stimulates progenitor differentiation. The cortex is generally smaller in schizophrenia patients, and understanding the global gene expression changes occurring during cortical development, and its relationship to genetic risk for schizophrenia, might reveal clues as to which genetic mechanisms are responsible for mediating the differences observed in patients. Our hypothesis is that neurodevelopmental diseases such as schizophrenia might share a genetic component with processes driving early cortical maturation, which can be modelled in vitro. Methods The CTX0E16 cell line was provided by ReNeuron and total RNA was extracted from proliferating neural progenitor cells (NPCs, n=3) and from cells that underwent a 28-day differentiation protocol (n=3). RNA samples were then processed on Illumina HT12 v4 chips. Raw fluorescence probe intensity values were extracted using GenomeStudio, and were subsequently background-corrected and log-transformed in R using the lumi package. Differentially expressed probes were determined using t-tests and the false-discovery rate of multiple testing correction was applied (q Results We expect to identify and annotate sets of genes involved in cortical maturation that are additionally involved in the aetiology of schizophrenia. Discussion The discussion will focus on the role of cortical maturation as a process that may be involved in schizophrenia aetiology.
Databáze: OpenAIRE
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