Ontology highlight
ABSTRACT:
PROVIDER: PRJNA949436 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23986429_1.fastq.gz | Fastqsanger.gz | |||
| SRR23986429_2.fastq.gz | Fastqsanger.gz | |||
| SRR23986430_1.fastq.gz | Fastqsanger.gz | |||
| SRR23986430_2.fastq.gz | Fastqsanger.gz | |||
| SRR23986431_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 40 |
Similar Datasets
Project description:SMPD4 (neutral sphingomyelinase-3/nSMase3) has recently been shown to be a new cause of microcephaly in a cohort of twenty-three pediatric patients. The function of nSMases in brain development and how SMPD4 variants cause human microcephaly and cerebellar hypoplasia was previously unknown.We developed an iPSC model to complement our mouse study. We found iPSC models from human SMPD4 patient and CRISPR/Cas9-induced SMPD4 knockout lines demonstrate a proliferation defect, increased cell death, loss of neural progenitors, and shortened primary cilia. Treatment with exogenous ceramide significantly rescues the cilia defect. SMPD4 patient and knockout cells have altered WNT signaling. We provide evidence that SMPD4 controls brain development by providing ceramide for primary ciliogenesis, suggesting a novel therapeutic strategy for SMPD4 mediated disease.
2023-12-24 | GSE250472 | GEO
Project description:Condensation of chromatin prior to enucleation is an essential component of terminal erythroid maturation, and defects in this process are associated with inefficient erythropoiesis and anemia. However, the mechanisms involved in this phenomenon are not well understood. Here, we identify a novel role for the histone variant H2A.X in erythropoiesis. We find in multiple model systems that this histone is essential for normal maturation and the loss of H2A.X in erythroid cells results in dysregulation in expression of erythroid specific genes as well a nuclear condensation defect. In Addition, we demonstrate that erythroid maturation is characterized by phosphorylation at both S139 and Y142 during late stage erythropoiesis. Knockout of the kinase BAZ1B/WSTF results in loss of Y142 phosphorylation and similar to loss of H2A.X, a defect in nuclear condensation. In this study, we present a model in which post-translational modifications on histone H2A.X during terminal erythroid maturation leads to Caspase-Induced Chromatin Condensation (CICC). In this novel pathway, although apoptosis is specifically suppressed, aspects of the apoptotic pathway remain active to drive terminal erythroid maturation. Suggesting that terminal erythroid maturation is indeed is a unique form of apoptosis.
2021-08-03 | GSE159422 | GEO
Project description:The associated publication describes a RUNX3-dependent defect in primary human CD34+ HSPC differentiation into the erythroid lineage. This study was designed to determine which genes are potential targets of RUNX3, and could contribute to regulation of erythropoiesis.
2019-03-01 | GSE119264 | GEO
Project description:Mutations in the minor spliceosome components such as RNU4atac, a small nuclear RNA (snRNA), are linked to primary microcephaly. We have reported that in the conditional knockout (cKO) mice for Rnu11, a minor spliceosome snRNA, minor intron splicing defect in minor intron-containing genes (MIGs) regulating cell cycle resulted in cell cycle defect with a concomitant increase in yH2aX+ cells and P53-mediated apoptosis. Trp53 ablation in the Rnu11 cKO mice did not prevent microcephaly. Although RNAseq analysis of the double knockout (dKO) pallium reflected transcriptomic shift towards the control from the cKO. We found elevated minor intron retention and alternative splicing across minor introns in the dKO. Disruption of these minor intron-containing genes (MIGs) resulted in cell cycle defect that was detected earlier and was more severe in the dKO, but with delayed detection of yH2aX+ DNA damage. Thus, P53 might also play a role in causing DNA damage in the developing pallium. In all, our findings further refine our understanding of the role of the minor spliceosome in cortical development and identify MIGs underpinning microcephaly in minor spliceosome-related disease.
2021-09-30 | GSE168366 | GEO
Project description:A new mouse model for congenital Zika infection in a wildtype, immunocompetent background employing intraplacental infection resulted in productive infection of embryonic brains and features of microcephaly during early development (E10.5-16.5). Gross morphological characterization showed translational relevance for understanding the viral neuropathogenesis and Zika-associated microcephaly in humans. Thus, an integrated, multi-omics (RNA-sequencing, proteomics) analysis of fetal brain tissues was performed to understand pathways perturbed by viral infection in developing brains. These analyses identified virus-induced defects in cell cycle progression and neurodevelopment, in S-phase DNA replication and NEUROD2/TBR2 transcription factor cascades, respectively. Among the most significant responses was induction of innate immune programs in ZIKV-infected brains, including immunoproteasome activation and MHC-I antigen display associated with immune cell infiltration and neuronal death during early development. Identification of specific components within major pathways contributing to viral infection-induced effects on neurodevelopment provides novel targets for therapeutic intervention against neurotropic infections and ZIKV-associated microcephaly specifically.
2021-08-21 | GSE118935 | GEO
Project description:A new mouse model for congenital Zika infection in a wildtype, immunocompetent background employing intraplacental infection resulted in productive infection of embryonic brains and features of microcephaly during early development (E10.5-16.5). Gross morphological characterization showed translational relevance for understanding the viral neuropathogenesis and Zika-associated microcephaly in humans. Thus, an integrated, multi-omics (RNA-sequencing, proteomics) analysis of fetal brain tissues was performed to understand pathways perturbed by viral infection in developing brains. These analyses identified virus-induced defects in cell cycle progression and neurodevelopment, in S-phase DNA replication and NEUROD2/TBR2 transcription factor cascades, respectively. Among the most significant responses was induction of innate immune programs in ZIKV-infected brains, including immunoproteasome activation and MHC-I antigen display associated with immune cell infiltration and neuronal death during early development. Identification of specific components within major pathways contributing to viral infection-induced effects on neurodevelopment provides novel targets for therapeutic intervention against neurotropic infections and ZIKV-associated microcephaly specifically.
2023-03-06 | MSV000091415 | MassIVE
Project description:D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion. Experiment Overall Design: Total RNA samples were prepared from head tissues from 2 embryos of Phgdh knockout and littermate wild-type controls. Experiment Overall Design: RNA of 4 biological replicates was hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.
2008-06-17 | E-GEOD-8555 | biostudies-arrayexpress
Project description:Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model
| PRJNA889388 | ENA
Project description:Interventions: Medical Device : After endoscopic removal of colon polyps larger than 2 cm, the mucosal defect is closured with a clips
Primary outcome(s): Complication ( delayed bleeding, delayed perforation, post electrocoagulation syndrome );Complication associated clipping ( hemorrhage, perforation)
Primary Purpose : Prevention, Intervention Model : Parallel, Blinding/Masking : Single, Blinding Target : Subject, Allocation : RCT
| 2727741 | ecrin-mdr-crc