Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA305612 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Whole genome sequencing of ATRX / TP53 knockdown clones of the neuroblastoma cell line SK-N-SH
| EGAS00001004550 | EGA
Project description:De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the underlying mechanisms remain elusive. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that on the one hand Chd8 stimulates the transcription of cell cycle genes, while on the other it precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of its expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the etiology of ASD.
2016-09-10 | GSE72442 | GEO
Project description:Periodontal ligament (PDL) stem-like cells (PDLSCs) are considered to be promising for the regeneration of periodontium because they demonstrate multipotency, high proliferative capacity, and potential to regenerate bone, cementum, and PDL tissue. However, the transplantation of autologous PDLSCs is restricted by limited availability and the need for tooth extraction to isolate these cells. PDLSCs are derived from neural crest cells (NCs) in early vertebrate development and NCs persist in adult PDL tissue. Therefore, we devised to promote the regeneration of periodontium by activating NCs to differentiate into PDLSCs and increasing their total number. SK-N-SH cells cultured on the extracellular matrix derived of human PDL cells (SK-PDLSCs) strongly expressed PDL-related marker genes and highly differentiated into mesenchymal lineage cells compared to untreated SK-N-SH cells. Expression levels of various hyaluronic acid (HA)-related genes were upregulated in induced pluripotent stem cells (iPSCs)-derived PDLSCs and SK-PDLSCs compared to iPSCs-derived NCs and SK-N-SH cells, respectively. Magnetic-activated cell sorting-assisted CD44-positive enrichment population of SK-N-SH cells showed higher expression of PDL-related marker genes after SK-PDLSCs induction than the CD44-negative population. Knockdown of CD44 in SK-N-SH cells significantly inhibited their ability to differentiate into SK-PDLSCs, while lower molecular HA (LHA) induction enhanced SK-PDLSC differentiation. LHA-containing electrospun nanofibrous membranes also promoted their SK-PDLSC differentiation. Our findings suggest that SK-N-SH cells are applied as a new model to induce the differentiation of NCs into PDLSCs. The LHA-CD44 relation is important for the differentiation of NCs into PDLSCs. LHA-containing electrospun nanofibrous membranes would promote the regeneration of periodontium by activating NCs in PDL tissue and increasing the total number of PDLSCs.
2023-06-27 | GSE235864 | GEO
Project description:Truncating mutations of CHD8, encoding a chromodomain helicase, and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA-seq) with genome-wide CHD8 binding (ChIP-seq). Suppressing CHD8 to levels comparable with loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated. CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8 binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (pM-BM- =M-BM- 1.01x10-9) and CHD8-bound genes (p = 4.34x10-3), which align with previously identified co-expression modules during fetal development. We also find an intriguing enrichment of cancer related gene-sets among CHD8-bound genes (p < 1.9x10-11). In vivo suppression of chd8 in zebrafish produced macrocephaly comparable to that of humans with inactivating mutations. These data indicate that heterozygous disruption of CHD8 precipitates a network of gene expression changes involved in neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis. ChIP-seq for CHD8 using three different antibodies, and the related protein CHD7, in human iPSC-derived NPCs treated with shRNA targeting GFP (which were used as control cells for an shRNA knockdown RNA-seq experiment that was part of the overall study)
2014-10-07 | E-GEOD-61487 | biostudies-arrayexpress
Project description:To understand the function of CHD8 in human ESC and neural differentiation, we generated the CHD8 knockout human ESCs and characterize the effect of loss-of-function of CHD8 on pluripotency maintenance and neuroectoderm determination by utilizing an efficient neuroectoderm differentiation protocol. Samples from hESC, CHD8KO_hESC and their derived-neural progenitor cells (hNPC) were collected for high-throughput sequencing with at least two replicates for each sample. Differentially expressed genes analysis showed loss of CHD8 affect the genes in ESC and NPC.
2021-10-19 | GSE171869 | GEO
Project description:Analysis of the effect of shRNA-mediated knockdown of TRPM7 on gene expression levels in SH-SY5Y and SH-EP2 human neuroblastoma cells. Results were used for the identification of neural-crest-associated transcription factors that were affected by TRPM7 knockdown. Total RNA isolated from SH-EP2 and SH-SY5Y human neuroblastoma cells transduced with a scrambled shRNA (control) or TRPM7 shRNA, experiment performed in duplicate.
2014-12-10 | E-GEOD-64000 | biostudies-arrayexpress
Project description:Whole-exome sequencing studies have implicated chromatin modifiers and transcriptional regulators in autism spectrum disorder (ASD) through the identification of de novo loss of function mutations in affected individuals. Many of these genes are co-expressed in mid-fetal human cortex, suggesting ASD risk genes converge in regulatory networks that are perturbed in ASD during neurodevelopment. To elucidate such networks we mapped promoters and enhancers bound by the chromodomain helicase CHD8, which is strongly enriched in ASD-associated de novo loss of function mutations, using ChIP-seq in mid-fetal human brain, human neural stem cells (hNSCs), and embryonic mouse cortex. We find that CHD8 targets are strongly enriched for ASD risk genes that converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in significant dysregulation of ASD risk genes targeted by CHD8, as well as additional genes important for neurodevelopment, including members of the Wnt/M-NM-2-catenin signaling pathway. Integration of CHD8 binding data with genetic and gene co-expression data in ASD risk models provides support for additional ASD risk genes. Together, our results suggest that loss of CHD8 function contributes to ASD through regulatory perturbation of other ASD risk genes during human cortical development. Two biological replicates for each ChIP with appropriate Input control Four biological replicates for each condition in knockdown experiments (Ctrl construct, Chd8 target C, and Chd8 target G)
2015-01-21 | E-GEOD-57369 | biostudies-arrayexpress
Project description:Human tissue based proteomics projects are challenging due to low abundance of proteins and tissue specificity of protein expression. In this study, we aimed to develop a cell-based approach to profile the male specific region of the Y chromosome (MSY) proteins. First, we profiled the expression of 23 Y chromosome genes and 15 of their X-linked homologues during neural cell differentiation from NT2 cells at three different developmental stages using qRT-PCR, western blotting and immunofluorescent (IF) techniques. The expression level of 12 Y-linked genes significantly increased over neural differentiation. Including RBMY1, EIF1AY, DDX3Y1, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. Subsequently, DDX3Y was selected as a candidate for knockdown as it was significantly expressed in neural progenitor cells and it is known to be expressed in a gender specific manner and play a role in spermatogenesis. A siRNA-mediated DDX3Y knockdown in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 920 reproducibly identified proteins detected, 74 proteins were differentially expressed following DDX3Y siRNA treatment compared to mock treated cells. Functional grouping indicated these proteins were associated with cell cycle, cell-to-cell signaling, apoptosis and other important networks such as RNA processing and transcription regulation. Disease-based analysis confirmed DDX3Y involvement primarily in neurological and RNA metabolism disorders. Our results confirm that MSY genes are expressed in male neuronal cells, and demonstrate that Y linked DDX3 (DDX3Y) could play a multifunctional role in neural cell development in a sexually dimorphic manner.
2015-09-17 | PXD002428 | Pride
Project description:Human tissue based proteomics projects are challenging due to low abundance of proteins and tissue specificity of protein expression. In this study, we aimed to develop a cell-based approach to profile the male specific region of the Y chromosome (MSY) proteins. First, we profiled the expression of 23 Y chromosome genes and 15 of their X-linked homologues during neural cell differentiation from NT2 cells at three different developmental stages using qRT-PCR, western blotting and immunofluorescent (IF) techniques. The expression level of 12 Y-linked genes significantly increased over neural differentiation. Including RBMY1, EIF1AY, DDX3Y1, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. Subsequently, DDX3Y was selected as a candidate for knockdown as it was significantly expressed in neural progenitor cells and it is known to be expressed in a gender specific manner and play a role in spermatogenesis. A siRNA-mediated DDX3Y knockdown in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 920 reproducibly identified proteins detected, 74 proteins were differentially expressed following DDX3Y siRNA treatment compared to mock treated cells. Functional grouping indicated these proteins were associated with cell cycle, cell-to-cell signaling, apoptosis and other important networks such as RNA processing and transcription regulation. Disease-based analysis confirmed DDX3Y involvement primarily in neurological and RNA metabolism disorders. Our results confirm that MSY genes are expressed in male neuronal cells, and demonstrate that Y linked DDX3 (DDX3Y) could play a multifunctional role in neural cell development in a sexually dimorphic manner.
2019-06-10 | MSV000083949 | MassIVE
Project description:The SH-SY5Y Human neuroblastoma cell line was subcloned from the SK-N-SH cell line, which has been isolated from a bone marrow biopsy of a 4 year-old female patient. To examine the overall distribution of gene expression under stress condition in human neuronal cells, we investigated changes in the transcriptome profiles in the SH-SY5Y cells depleted with ERRαlpha and ERRgamma by gene knockdown. We detected changes in the expression levels for several genes.
2024-08-20 | GSE208270 | GEO