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Gene expression analysis of transplanted hiPSC-astrocyte progenitors generated from monozygotic twin pair discordant for schizophrenia into mouse brain

ABSTRACT: The humanized mice's frontal cortical tissues were used for transcriptomic analysis, as this brain area shows early involvement in pathophysiology of schizophrenia. We transplanted hiPSC-astrocyte progenitors from one monozygotic twin pair discordant for schizophrenia and one healthy control into neonatal mouse forebrains and analyzed mouse behavior at five and ten months, followed by gene expression profiling of the frontal cortices seven days later.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE191249 | GEO | 2021/12/20

REPOSITORIES: GEO

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Project description:The expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences. Keywords: Monozygotic twin pair Expression Profiles Genome-wide gene expression in lymphoblastoid cell lines was determined using microarrays derived from 15 monozygotic (MZ) twin pairs (10 male, 9 female). 10 twin pair are discordant, 4 are concordant for a disease phenotype and their are 5 controls which have no disease phenotype. This data set was analyzed to interrupt replicated effects of sex and genotype, not disease characteristics. Subsets of these samples have been analyzed separately for disease characteristics, (GSE7036 M-bM-^@M-^S 3 MZ twins discordant for bipolar disorder) and (GSE7486 - 5 discordant and 4 concordant MZ twin pairs with idiopathic absence epilepsies and 5 unaffected MZ twin pairs).

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Gene expression analysis of transplanted hiPSC-astrocyte progenitors generated from monozygotic twin pair discordant for schizophrenia into mouse brain

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