Project description:We compare fore- and mid-brain transcriptomes of reproductive males in monogamous and non-monogamous species pairs of Peromyscus mice, Microtus voles, parid songbirds, dendrobatid frogs, and Xenotilapia species of cichlid fishes. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates.
Project description:Chronic stress increases the risk of emotional disorders by altering brain structure and function. Patients with post-traumatic stress disorder (PTSD) or depressions show activity difference between the two hemispheres in the prefrontal cortex (PFC) but molecular targets associated with this laterality remains unclear. Here, we reveal that chronic social defeats later gene-expression profile differentially between the left and right medial prefrontal cortices (mPFC) in mice.
Project description:Although the loss or reversal of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile post-mortem brain samples from subjects with SCZ, psychotic BD [BD(+)] or non-psychotic BD [BD(-)], or matched controls (n=10/group, corresponding to different brain hemispheres) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (n=3-4/group) to identify pathways associated with SCZ or BD(+) and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (n=35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q<0.25) coordinately upregulated in both SCZ and BD(+), and glutamate signaling and TGFβ signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD(+) patients, and Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p=0.0012). While lateralized expression of TGFB2 in controls (p=0.017) is associated with a corresponding change in DNAM (p≤0.023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss or reversal of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFβ signaling, indicating potential avenues for disease prevention/treatment.
Project description:Although the loss or reversal of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile post-mortem brain samples from subjects with SCZ, psychotic BD [BD(+)] or non-psychotic BD [BD(-)], or matched controls (n=10/group, corresponding to different brain hemispheres) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (n=3-4/group) to identify pathways associated with SCZ or BD(+) and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (n=35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q<0.25) coordinately upregulated in both SCZ and BD(+), and glutamate signaling and TGFβ signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD(+) patients, and Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p=0.0012). While lateralized expression of TGFB2 in controls (p=0.017) is associated with a corresponding change in DNAM (p≤0.023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss or reversal of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFβ signaling, indicating potential avenues for disease prevention/treatment.
Project description:East African cichlid fishes have radiated in an explosive fashion. The (epi)genetic basis for the abundant phenotypic diversity of these fishes remains largely unknown. As transposable elements (TEs) contribute extensively to genome evolution, we reasoned that TEs may have fuelled cichlid radiations. While TE-derived genetic and epigenetic variability has been associated with phenotypic traits, TE expression and epigenetic silencing remain unexplored in cichlids. Here, we profiled TE expression in African cichlids, and describe dynamic expression patterns during embryogenesis and according to sex. Most TE silencing factors are conserved and expressed in cichlids. We describe an expansion of two truncated Piwil1 genes in Lake Malawi/Nyasa cichlids, encoding a Piwi domain with catalytic potential. To further dissect epigenetic silencing of TEs, we focused on small RNA-driven epigenetic silencing. We detect a small RNA population in gonads consistent with an active Piwi-interacting RNA (piRNA) pathway targeting TEs. We uncover fluid genomic origins of piRNAs in closely related cichlid species. This, along with signatures of positive selection in piRNA pathway factors, points towards fast co-evolution of TEs and the piRNA pathway. Our study is the first step to understand the contribution of ongoing TE-host arms races to the cichlid radiations in Africa.