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Transcriptome analysis of the facial processes in Rspo2, WNT9b and Rspo2;Wnt9b double mutant mice

ABSTRACT: Purpose: To determine transcriptome profile of the facial processes of Wnt9b, Rspo2 and double gene knockout embryos by NG RNA sequencing Method: Embryonic facial process RNA samples isolated from wild type, Rspo2, Wnt9b and Rspo2;Wnt9b double mutants in triplicate (except wild type (n=2)) at embryonic day 10.5 Results: single-end 50bp reads, 19.8 million reads - 30.7 million reads.

ORGANISM(S): Mus musculus

PROVIDER: GSE147474 | GEO | 2020/03/25

REPOSITORIES: GEO

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Transcriptome analysis of the facial processes in Rspo2, WNT9b and Rspo2;Wnt9b double mutant mice

Project description:Transcriptome analysis of the facial processes in Rspo2, WNT9b and Rspo2;Wnt9b double mutant mice

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KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3 [snRNA-seq]

Project description:Intellectual disability (ID) affects ~2% of the population and ID-associated genes are enriched for epigenetic factors, including those encoding the largest family of histone lysine acetyltransferases (KAT5-KAT8). Among them is KAT6A, whose mutations cause KAT6A Syndrome, with ID as a common clinical feature. However, the underlying molecular mechanism remains unknown. Here, we find that KAT6A deficiency impairs synaptic structure and plasticity in hippocampal CA3, but not in CA1 region, resulting in memory deficits in mice. We further identify a CA3-enriched gene Rspo2, encoding Wnt activator R-spondin 2, as a key transcriptional target of KAT6A. Importantly, deletion of Rspo2 in excitatory neurons impairs memory formation, and restoring RSPO2 expression in CA3 rescues the deficits in Wnt signaling and learning-associated behaviors in Kat6a mutant mice. Collectively, our results demonstrate that KAT6A-RSPO2-Wnt signaling plays a critical role in regulating hippocampal CA3 synaptic plasticity and cognitive function, providing potential therapeutic targets for KAT6A Syndrome and related neurodevelopmental diseases.

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Project description:R-spondins (Rspos) comprise a family of four secreted proteins that have important roles in cell proliferation, cell fate determination and organogenesis. Rspos typically exert their effects by potentiating the Wnt/β-catenin signaling pathway. To systematically investigate the impact of Rspo/Wnt on gene expression, we performed a microarray analysis using C57MG mouse mammary epithelial cells treated with recombinant Rspo2 and/or Wnt3a. This study compares gene expression in C57MG cells after 24h treatment with recombinant Rspo2 and recombinant Wnt3a alone or in combination versus BSA treatment. Control cells were treated with BSA, since it was used as carrier for the recombinant proteins. Each treatment was done in biological triplicate.

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Project description:Recent developments in molecular programming of mesodiencephalic dopaminergic (mdDA) neurons have led to the identification of many transcription factors playing a role in mdDA specification. LIM homeodomain transcription factor Lmx1a is essential for chick mdDA development, and for the efficient differentiation of ES-cells towards a dopaminergic phenotype. In this study, we aimed towards a more detailed understanding of the subtle phenotype in Lmx1a-dr/dr mice. Therefore, microarray analysis was performed, to elucidate the exact molecular programming underlying the neuronal deficits after loss of Lmx1a. Subsequent expression analysis confirmed that Nurr1 is regulated by Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral loss of expression of most of these genes during development, Nurr1 and C130021l20Rik were affected in the SNc of the mature mdDA system. Interestingly, this deficit was marked by the complete loss of the Wnt/b-catenin signaling activator Rspo2 in this domain. Expression analysis in Rspo2-/- embryos revealed affected mdDA neurons, partially phenocopying the Lmx1a mutant. Together, in this study we reveal that Lmx1a is essential for a rostral-lateral subset of the mdDA neuronal field, where it might serve a critical function in modulating proliferation and differentiation of mdDA progenitors through the activation of the Wnt activator Rspo2. Microarray expression study comparing 4 samples of homozygous LMX1A dr/dr mice, midbrain E12.5 with a pooled sample of their wt/wt littermates. Two samples were analyzed in opposite dye orientation.

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Discovery of cis-spliced chimeric RNAs between adjacent genes in human prostate cells

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