Dosage Counts: Correcting Trisomy-21-Related Phenotypes in Human Organoids and Xenografts.

Dosage Counts: Correcting Trisomy-21-Related Phenotypes in Human Organoids and Xenografts. Cell Stem Cell. 2019 Jun 06;24(6):835-836 Authors: Manley WF, Anderson SA 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

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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
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
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
Abstract Trisomy 21 (T21), Down Syndrome (DS) is the most common genetic cause of dementia and intellectual disability. Modeling DS is beginning to yield pharmaceutical therapeutic interventions for amelioration of intellectual disability, which are currently being tested in clinical trials. DS is also a unique genetic system for investigation of pathological and protective mechanisms for accelerated ageing, neurodegeneration, dementia, cancer, and other important common diseases. New drugs could be identified and disease mechanisms better understood by establishment of well‐controlled cell model systems. We have develop...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research
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Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research
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