Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in Christianson Syndrome cell model

ABSTRACT: Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in Christianson Syndrome cell model

PROVIDER: PRJNA1032154 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26528100_1.fastq.gz	Fastqsanger.gz
	SRR26528100_2.fastq.gz	Fastqsanger.gz
	SRR26528101_1.fastq.gz	Fastqsanger.gz
	SRR26528101_2.fastq.gz	Fastqsanger.gz
	SRR26528102_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 108

Similar Datasets

Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in Christianson Syndrome cell model

Project description:To investigate the function NHE6 protein, we established HAP1 CRISPR-CAS9 SLC9A6 Knockout lines and their paired controls . We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells, each with 6 replicates, at two time points.

2023-10-30 | GSE246263 | GEO

Bioresponsive lysosome-targeting chimeras for targeted protein degradation

Project description:Lysosome-mediated degradation of extracellular proteins represents an emerging therapeutic paradigm that exploits cellular waste-disposal machinery to eliminate pathogenic targets. Despite its promise, achieving selective degradation of disease-associated proteins remains constrained by the scarcity of discovering highly effective disease-specific lysosome-targeting receptors. To address this limitation, we engineered NeuroTAC, a lysosome-targeting chimera (LYTAC) that bridges a sortilin-binding ligand-neurotensin (NT) to a disease-specific antibody targeting proteins overexpressed in tumors and inflammatory disorders. NeuroTAC demonstrated robust degradation efficacy against both membrane-bound and extracellular proteins in experimental models. Leveraging the dysregulated activity of matrix metalloproteinases (MMPs), a characteristic feature of tumor and inflammatory microenvironments, we further developed BioresTAC as an innovative bioresponsive LYTAC variant. This advanced construct integrates an MMP-cleavable linker and terminal RGD peptides, enabling MMP-triggered activation and spatial precision in MMP-enriched pathological niches. Systematic validation demonstrated that NeuroTAC and BioresTAC mediate broad-spectrum protein degradation with microenvironmental selectivity, enhancing therapeutic efficacy in cancer and psoriasis models. These findings advance the translational potential of lysosome-engaging biologics, offering a dual strategy for precision degradation through receptor recruitment and microenvironmental sensing.

2025-05-01 | GSE295826 | GEO

Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.

Project description:Christianson syndrome (CS) is an X-linked disorder resulting from loss-of-function (LoF) mutations in SLC9A6 encoding the endosomal Na+/H+ exchanger 6 (NHE6). CS presents with developmental delay, seizures, intellectual disability, nonverbal status, postnatal microcephaly, and ataxia. To define transcriptome signatures of NHE6 LoF, we conducted in-depth RNA-sequencing (RNA-seq) analysis on a haploid NHE6 null cell model. CRIPSR/Cas9 genome editing introduced multiple LoF mutations into SLC9A6 in the near haploid human cell line Hap1. Isogenic, paired parental controls were also studied. NHE6 mutant cell lines were confirmed to have intra-endosomal over-acidification as was seen in other NHE6 null cells. RNA-seq analysis was performed by two widely used pipelines: HISAT2-StringTie-DEseq2 and STAR-HTseq-DEseq2. We identified 1056 differentially expressed genes in mutant NHE6 lines, including genes associated with neurodevelopment, synapse function, voltage-dependent calcium channels, and neuronal signaling. Weighted gene co-expression network analysis was then applied and identified a critical module enriched for genes governing lysosome function. By identifying significantly changed gene expression that is associated with lysosomal mechanisms in NHE6-null cells, our analyses suggest that loss of NHE6 function may converge on mechanisms implicated in lysosome-related neurologic disease. Further, this haploid cell model will serve as an important tool for translational science in CS.

| S-EPMC10695175 | biostudies-literature

Bioresponsive lysosome-targeting chimeras for targeted protein degradation

Project description:Bioresponsive lysosome-targeting chimeras for targeted protein degradation

| PRJNA1256450 | ENA

INTS8 mutations cause severe neurodevelopmental syndrome

Project description:Integrator (INT) is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. INT has at least 14 subunits, but INT germline mutations causing human disease have not been reported. We identified mutations in the Integrator Complex Subunit 8 gene (INTS8) causing a rare neurodevelopmental syndrome. In patient cells we identified significant disturbance of gene expression and RNA processing. Also, we show that injection of ints8 oligonucleotide morpholinos into zebrafish embryos leads to prominent underdevelopment of the head demonstrating the evolutionary conserved requirement of INTS8 in brain development. RNA sequencing was carried out using RNA samples from fibroblasts from two individuals with germline bi-allelic INTS8 mutations and from two healthy individuals

2017-05-17 | E-GEOD-76878 | biostudies-arrayexpress

Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus

Project description:Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in the microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial ribosomal integrity and proteostasis. Our Drosophila studies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteostasis perturbations, either by genetic or environmental factors, are a pathogenic mechanism for neurodevelopmental disorders.

2022-02-17 | PXD025289 | Pride

Integrative analysis identifies key molecular signatures underlying neurodevelopmental deficits in fragile X syndrome

Project description:Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by epigenetic silencing of FMR1 and loss of FMRP expression. Here we describe the establishment of an isogenic human pluripotent embryonic stem cell model of FXS. Using CRISPR/Cas9 to introduce indels in exon 3 of FMR1 and result in complete loss of FMRP (FMR1KO). We show that FMRP-deficient neurons exhibit a number of phenotypic abnormalities including neurite outgrowth and branching deficits and impaired electrophysiological network activity as measured by multi-electrode arrays. RNA-Seq and proteome analysis of FMRP-deficient neurons revealed transcriptional dysregulation in pathways related to neurodevelopment, neurotransmission, and the cell cycle.

2020-06-18 | PXD011630 | Pride

INTS8 mutations cause severe neurodevelopmental syndrome

2017-05-17 | GSE76878 | GEO

Integrative Analysis Identifies Key Molecular Signatures Underlying Neurodevelopmental Deficits in Fragile X Syndrome

Project description:Integrative Analysis Identifies Key Molecular Signatures Underlying Neurodevelopmental Deficits in Fragile X Syndrome

| PRJNA481532 | ENA

Integrative Analysis Identifies Key Molecular Signatures Underlying Neurodevelopmental Deficits in Fragile X Syndrome

Project description:We report the generation of isogenic hPSC model of FXS and characterize the neurodevelopmental capacity of these cells, performed transcriptome profiling in FXS neurons and identified key pathways

2020-05-24 | GSE117248 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data