GSE125837 Silencing Trisomy 21 with XIST in Neural Stem Cells Promotes Neuronal Differentiation (bulk)

Contributors : Jan T Czerminski ; Jeanne B LawrenceSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlthough Down Syndrome (DS) is the leading genetic cause of intellectual disability in children, the developmental pathogenesis remains largely unknown, and better strategies are needed to investigate this. We previously showed that one copy of chromosome 21 can be epigenetically silenced in DS iPSCs by insertion of an XIST transgene, which produces a non-coding RNA that normally silences one X chromosome in female cells. XIST was shown to induce heterochromatin and silence transcription across chromosome 21 in pluripotent stem cells, the natural developmental context of XIST function. Prior literature indicated that initiation of chromosome silencing is only possible within 48 hours of mES cell differentiation, however it would be highly advantageous experimentally if trisomy silencing could be initiated in differentiated cells, and this is critical for any therapeutic potential of XIST. Here we use RNAseq and molecular cytology to investigate the effectiveness of XIST for trisomy silencing in cells undergoing in vitro neural differentiation and examine the potential cell phenotypic effects of chromosomal silencing. Induction of XIST from the onset of differentiation resulted in comprehensive silencing of chromosome 21 genes, providing a powerful approach to examine effects of trisomy on neurogenesis. To determine whether human neural stem...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze), but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the genes that were unique...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Receptor-interacting protein 140 (RIP140) is a transcription co-regulator of several transcription factors and a signal transduction regulator. RIP140 was recently implicated in the regulation of cognitive functions. The gene that encodes RIP140 is located on chromosome 21. An increase in RIP140 expression was observed in the fetal cerebral cortex and hippocampus in Down syndrome patients who exhibited strong cognitive disabilities. We hypothesized that RIP140 overexpression affects cognitive function in adult neural development. The present study used a Cre-dependent adeno-associated virus to selectively...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research
American Journal on Intellectual and Developmental Disabilities,Volume 125, Issue 2, Page 90-92, March 2020.
Source: American Journal on Intellectual and Developmental Disabilities - Category: Disability Authors: Source Type: research
Contributors : Jan T Czerminski ; Jeanne B LawrenceSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlthough Down Syndrome (DS) is the leading genetic cause of intellectual disability in children, the developmental pathogenesis remains largely unknown, and better strategies are needed to investigate this. We previously showed that one copy of chromosome 21 can be epigenetically silenced in DS iPSCs by insertion of an XIST transgene, which produces a non-coding RNA that normally silences one X chromosome in female cells. XIST was shown to induce heterochromatin and silence transcription...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Abstract Studies in mice suggest that Olig2 gene dosage alters cerebral cortical interneuron development and contributes to trisomy-21/Down-syndrome-related intellectual disability. Xu et al. (2019) extend these studies through the remarkable use of cerebral organoid and human iPSC/mouse brain chimera experimental systems that provide an opportunity for the development of novel therapeutics. PMID: 31173710 [PubMed - in process]
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT. Introduction Rett syndrome (RTT) is a progressive neurodevelopmental disorder. It primarily affects females, who show the first obvious symptoms within 6–18 months after birth. Among the characteristics are a regression of mental ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
AbstractDown syndrome (DS) or trisomy 21 (T21) is a leading genetic cause of intellectual disability. To gain insights into dynamics of molecular perturbations during neurogenesis in DS, we established a model using induced pluripotent stem cells (iPSC) with transcriptome profiles comparable to that of normal fetal brain development. When applied on iPSCs with T21, transcriptome and proteome signatures at two stages of differentiation revealed strong temporal dynamics of dysregulated genes, proteins and pathways belonging to 11 major functional clusters. DNA replication, synaptic maturation and neuroactive clusters were di...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Contributor : Jiang PengSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDown syndrome (DS), caused by triplication of human chromosome 21 (HSA21), is the most common genetic origin of intellectual disability. Despite the limited success of current pharmacological interventions, little has been achieved to reverse the abnormal brain developmental in DS. Here, using human induced pluripotent stem cell (hiPSC)-based brain organoid and in vivo human neuronal chimeric mouse brain models, we demonstrate that the HSA21 genes OLIG1 and OLIG2 exhibit distinct temporal expression patterns durin...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
ConclusionWe established the cellular models of DS patients and derived differentiation into different cell types in vitro, which has the similar function with patient HSCs. On the basis of that, we found has_circ_0082802 may play important role in erythroid differentiation. We can further search for the potential drug targets thateffective against leukemia of DS patients. This approach would provide a powerful cell resource for clinical research and a useful model for the study of the mechanisms of DS-AMLDisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 501. Hematopoietic Stem and Progenitor Biology Source Type: research
NEUROGENESIS IMPAIRMENT: AN EARLY DEVELOPMENTAL DEFECT IN DOWN SYNDROME. Free Radic Biol Med. 2017 Jul 26;: Authors: Stagni F, Giacomini A, Emili M, Guidi S, Bartesaghi R Abstract Down syndrome (DS) is characterized by brain hypotrophy and intellectual disability starting from early life stages. Accumulating evidence shows that the phenotypic features of the DS brain can be traced back to the fetal period since the DS brain exhibits proliferation potency reduction starting from the critical time window of fetal neurogenesis. This defect is worsened by the fact that neural progenitor cells exhibit redu...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
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