Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation and characterization of NGLY1 patient-derived midbrain organoids

ABSTRACT: Generation and characterization of NGLY1 patient-derived midbrain organoids

PROVIDER: PRJNA930476 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23310364_1.fastq.gz	Fastqsanger.gz
	SRR23310364_2.fastq.gz	Fastqsanger.gz
	SRR23310365_1.fastq.gz	Fastqsanger.gz
	SRR23310365_2.fastq.gz	Fastqsanger.gz
	SRR23310366_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

Generation and characterization of NGLY1 patient-derived midbrain organoids

Project description:NGlY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder, and liver dysfunction. To better understand disease pathogensis and neurological symptoms of NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with disease causing mutations.

2023-02-03 | GSE224294 | GEO

Generation and characterization of NGLY1 patient-derived midbrain organoids.

Project description:NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations-one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency.

| S-EPMC9978932 | biostudies-literature

Microarray-based Gene Expression Analysis of WA09 human cerebral organoids with CRISPR-KO of NGLY1

Project description:Analysis of human cerebral organoids developed from both WA09 human embryonic stem cells with CRISPR-KO of NGLY1. The hypothesis tested was that NGLY1 is key to normal human brain development and when knocked out would alter cerebral development of organoids through the differential expression of various key genes.

2022-04-19 | GSE169696 | GEO

Transcriptome profiling of DA neurons, human midbrain-like organoids and prenatal midbrain

Project description:Recent advances in three dimensional (3D) culture systems have led to the generation of brain organoids that share resemblance to different parts of the human brains; however, a 3D organoid model of the midbrain that contains functional midbrain dopaminergic (mDA) neurons has not been reported. In this study, we develop a method to differentiate human PSCs into a large multicellular organoid-like structure that contains distinct layers of neuronal cells with a transcriptomic profile that resembles human prenatal midbrain. Importantly, we detected electrically active and functionally mature mDA neurons, and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using non-3D methods or in the MLOs generated from mouse embryonic stem cells, our human MLOs uniquely produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a novel tractable in vitro system to study the human midbrain and its related diseases.

2016-08-24 | E-MTAB-4868 | biostudies-arrayexpress

Single cell RNA sequencing profile of 60 day old human iPSC-derived midbrain organoids from healthy individual, Parkinson’s disease patient (Miro1 p.R272Q mutation) and its isogenic control

Project description:Use of patient specific models, such as midbrain organoids, have shown to be valuable tools to models Parkinson’s disease as well as to identify novel pathological cellular and molecular mechanisms. In here, we used single cell RNA sequencing analysis of 60 day old midbrain organoids obtained from a Parkinson’s disease patient carrying the p.R272Q Miro1 mutation, its isogenic control and a healthy control to explore the effect of RhoT1 gene in different cellular populations present within the midbrain organoids (e.g. dopaminergic neurons, astrocytes) and the subsequent effect on the PD pathology.

2025-01-30 | GSE264097 | GEO

NGLY1 mutations cause protein aggregation in human neurons

Project description:Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy and seizures. NGLY1’s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons, but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.

2025-02-13 | GSE197454 | GEO

Gene expression profile of healthy control organoids, a Parkinson disease patient specific midbrain organoid carrying a triplication in the SNCA gene and two healthy control organoids co-cultured with either healthy or PD hindbrain organoids

Project description:Single nuclei RNAseq was used to characterize the cell diversity in healthy control hindbrain organoids, as well as in PD midbrain organoids. Sequencing of healthy midbrain organoids after co-culture with either healthy or PD hinbrain organoids was used to compare the influence of the healthy versus the disease hindbrain context to the healthy midbrain model.

2025-04-01 | GSE275820 | GEO

Transcriptome profiling of NGLY1 deficient K562 cells

Project description:The data includes a transcriptome analysis of K562 cell lines in which the gene N-glycanase 1 (NGLY1) was mutated in exon 1 and/or exon 3 to include loss of function mutations as described in Mueller and Jakob et al, 2020. The data were used in conjunction with whole proteome MS/MS experiments to show a gene expression profile consistent with NGLY1 deficiency, a human disease. The experiments demonstrate the wide ranging effect of the loss of NGLY1 on a cellular system.

2020-04-20 | E-MTAB-8876 | biostudies-arrayexpress

Modeling PD in midbrain-like organoids

Project description:Modeling PD in midbrain-like organoids

| PRJNA525884 | ENA

Modelling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids

Project description:Recent advances in generating 3 dimensional (3D) organoid systems from stem cells offer new possibilities for disease modeling. In this study, we generate isogenic 3D midbrain organoids with or without a Parkinson’s disease-associated LRRK2 G2019S mutation. LRRK2-G2019S midbrain organoids derived from LRRK2 targeted human iPSCs in vitro have LRRK2-associated sporadic Parkinson's disease phenotypes. Midbrain-like 3D organoids expressing LRRK2-G2019S showed dynamic changes in globle gene expression.

2019-02-02 | GSE125234 | 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