A mouse model of DS-ALL
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ABSTRACT:
PROVIDER: PRJEB68384 | ENA |
REPOSITORIES: ENA
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Project description:Down syndrome (DS) results from trisomy of human chromosome 21 (HSA21), and DS research has been greatly advanced by the use of mouse models. We previously generated a humanized mouse model of DS, TcMAC21, which carries the long arm of HSA21. These mice exhibit learning and memory deficits, and may reproduce neurodevelopmental alterations observed in humans with DS. Here we performed histologic studies of the TcMAC21 forebrain from embryonic to adult stages. The TcMAC21 neocortex showed reduced proliferation of neural progenitors and delayed neurogenesis. These abnormalities were associated with a smaller number of projection neurons and interneurons. Further, (phospho-)proteomic analysis of adult TcMAC21 cortex revealed alterations in the phosphorylation levels of a series of synaptic proteins. The TcMAC21 mouse model shows similar brain development abnormalities as DS, and will be a valuable mode to investigate prenatal and postnatal causes of intellectual disability in humans with DS.
2023-10-23 | PXD044343 | Pride
Project description:Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al. reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twin’s fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. In addition, an independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS. Ts65Dn mouse model of DS
2015-02-21 | E-GEOD-64840 | biostudies-arrayexpress
Project description:Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al. reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twin’s fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. In addition, an independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS.
2015-02-21 | GSE64840 | GEO
Project description:Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas, (2) Mutant Braf mouse model melanomas from UVR exposed mice and (3) Mutant Braf mouse model melanomas from UVR exposed, sunscreen protected mice.
| EGAS00001000729 | EGA
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.
2010-08-01 | GSE16677 | GEO
Project description:Bacillus safensis strain:DS-1 | isolate:DS-1 Genome sequencing
| PRJNA1142686 | ENA
Project description:Efforts to advance RNA aptamers as a novel therapeutic modality have been limited by their susceptibilty to degradation and immunogenicity. In a previous study, we demonstrated synthesized double-stranded circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated Protein Kinase R (PKR). Here, we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon alpha (IFNα)/dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.
2024-03-04 | GSE248678 | GEO
Project description:Janthinobacterium sp. DS Genome sequencing and assembly
| PRJNA721696 | ENA
Project description:In this study we performed a systematic analysis of the non-coding RNA (ncRNA) transcriptomes of the Down Syndrome (DS) developing hippocampus using the DS mouse model Dp16(1)Yey. DS, caused by the trisomy of chromosome 21 (HSA21) is the most frequent human chromosomal disorder. Hippocampal-dependent learning and memory impairment is one of the most significant deficits of DS. ncRNAs: microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) have been increasingly revealed to be participating in various biological activities, especially in the brain development and neuronal functions. This study provides a map of the dysregulated lncRNAs and circRNAs in the DS developing hippocampus for the first time.
2020-05-31 | GSE120801 | GEO
Project description:Down syndrome (DS), a genetic condition leading to intellectual disability, is characterized by triplication of human chromosome 21. Neuropathological hallmarks of DS include abnormal central nervous system development that manifests during gestation and extends throughout life. As a result, newborns and adults with DS exhibit cognitive and motor deficits and fail to meet typical developmental and lack independent life skills. In the last two decades, a number of preclinical treatment studies showed beneficial effects in the Ts65Dn mouse model. As of summer 2020, 13 pharmacological interventions have been tested with little evidence of success in humans with DS. Potential reasons for this failure may be related to the fact that these therapeutic interventions were carried out too late, and not during the prenatal and early postnatal critical periods for brain development. To date, no prenatal treatment studies have been reported in pregnant women carrying fetuses with T21. A limited number of prenatal treatment studies using fluoxetine, maternal choline supplementation and the neuroprotective peptides NAP and SAL have been described using the Ts65Dn mouse model of DS. In our previous studies, we integrated gene expression data from nine different cellular and tissue sources in both humans with DS and mouse models to identify common dysregulated signaling pathways and cellular processes. We demonstrated that pathway abnormalities associated with DS were the result of gene-dosage specific effects and the consequence of a global stress response with activation of compensatory mechanisms. To counteract these genome-wide abnormalities, we used the Connectivity Map database (www.broadinstitute.org/CMap) to discover molecules that could be repurposed to rescue the transcriptome and promote more typical brain development in individuals with DS. One of the molecules that had the most consistent negative scores (hence, negating the dysregulated gene expression signatures in DS) across tissues and species was apigenin (4’, 5, 7-trihydroxyflavone). Here, we hypothesized that prenatal treatment with apigenin would partly rescue the global gene expression dysregulation to improve neurogenesis and postnatal cognitive outcomes in DS. In the current study, we used a human in vitro cell model (amniocytes derived from live fetuses with Trisomy 21 and euploid fetuses) and the Ts1Cje mouse model of DS to evaluate the effects of apigenin as a potential therpay for prenatal brain defects and postnatal cognitive outcome in DS. We demonstrated that apigenin is a safe treatment that can rescue oxidative stress and total antioxidant capacity imbalance in human amniocytes from fetuses with T21. It also improved several postnatal behavioral deficits in the Ts1Cje mouse model. We also showed that apigenin achieves its therapeutic action by triggering the expression of neurogenic genes, suppressing inflammation via inhibiting NFκB and by reducing the production of pro-inflammatory cytokines, while promoting the production of anti-inflammatory cytokines, angiogenic and neurotrophic factors.
2020-09-23 | GSE158376 | GEO