Project description:The autism spectrum disorders (ASD) are a collection of disorders with heterogeneous etiology, exhibiting common traits including impaired social interactions and communications, repetitive behaviors. 15q11-q13 copy number variations (CNV) were found in 1-3% of ASD cases; of which the detailed mechanism of the major contributor UBE3A gene acted still remained elusive. Here we identified a key enzyme in RA synthesis, negatively regulated in ubiquitination-dependent mode promoted by UBE3A. Our data provide evidences linking UBE3A hyperactivity with ASD phenotypes, with implications for understanding ASD etiology and providing potential interventions in ASD clinical therapy.
Project description:Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile 18 patient glioblastomas by single cell RNA sequencing (scRNAseq). From this, we uncovered two principal cell-of-origin relations. Each lineage displays unique directional differentiation trajectories and transcriptional cores from the naïve cell populations. Thus, glioblastoma is defined by robust cell lineage features which may provide insights into the cell origin of the diseases.
Project description:∆FosB epigenetically regulates target gene expression; however, whether ∆FosB targets the same genes when induced by recurrent seizures in different neurological conditions like Alzheimer's disease (AD) is unclear. We performed hippocampal ChIP-sequencing to identify ∆FosB target genes in APP mice, a model of AD, and in pilocarpine-treated wildtype mice (Pilo mice), a model of epilepsy. Functional domains modulated by ∆FosB target genes are expanded and diversified in APP mice and in Pilo mice (vs respective controls), and primarily involve neuronal excitability and neurotransmission, neurogenesis, chromatin remodeling, and cellular stress and immunity. To identify genes bound by ∆FosB regardless of seizure etiology, we focused on the 442 ∆FosB target genes in both APP and Pilo mice (not respective controls), which related to pathways including membrane potential regulation, glutamatergic signaling, complement activation, neuron-glia population maintenance, and chromatin dynamics. RNA-sequencing and RT-qPCR in independent mice detected altered expression of several ∆FosB targets shared in APP and Pilo mice. Our findings indicate that seizure-induced ∆FosB can bind genes in seizure etiology-dependent patterns, but can also bind genes in patterns regardless of seizure etiology. Understanding factors that influence ∆FosB binding patterns could reveal novel insights into control of gene expression in disorders with recurrent seizures.
Project description:Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile control and genetically modified human brain perivasuclar fibroblasts by single cell RNA sequencing (scRNAseq). From this, we observed the potential tumorigenicity of brian perivascular fibroblasts.
Project description:This project aims at comparing endometrium from women with and without endometriosis during the secretory phase of menstrual cycle. The present results constitute a first step towards identifying potential diagnosis biomarkers and may provide a better understanding of endometriosis especially the etiology of the disease.
