Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omics Evaluation of Human iPSCs and iPSC-derived Neurons

ABSTRACT: The granulin (GRN) gene stands out as a prominent player in frontotemporal degeneration (FTD). Progranulin (PGRN) is a protein encoded by the GRN gene. Mutations in the GRN gene leading to PGRN deficiency are associated with lysosomal storage diseases and various neurodegenerative diseases. Despite the significance of GRN function, the specific impact of GRN-/- condition on diverse biomolecules such as proteins, lipids, and metabolites remain unclear. This study employs a multi-omics approach, integrating proteomics, lipidomics, and metabolomics analyses for comprehensively unraveling the molecular alterations by GRN-/- condition. Proteins, lipids, and metabolites were obtained from the same sample using a single extraction method. Our result reveals distinct molecular profiles between iPSC and neurons, emphasizing upregulated synaptic proteins such as SYN1, SYT1, VAMP2, and SV2A in proteomics, decreased cardiolipin (CL) containing 16:0 and 18:1 acyl chain in lipidomics, and shifts in acetylcholine and amino acid in metabolomics. Furthermore, the GRN-/- condition induces significant alterations across the proteome, lipidome, and metabolome of induced pluripotent stem cells (iPSC) and iPSC-derived neurons, unveiling unique metabolic pathways. Although this study was conducted at a whole cell level, this comprehensive perspective contributes to our understanding of the intricate interplay among proteins, lipids, and metabolites in neurodevelopment and neurodegenerative diseases.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Ling Hao

PROVIDER: MSV000093388 | MassIVE | Mon Nov 13 16:17:00 GMT 2023

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

GNPS - Multi-omics Evaluation of Human iPSCs and iPSC-derived Neurons

Project description:The granulin (GRN) gene stands out as a prominent player in frontotemporal degeneration (FTD). Progranulin (PGRN) is a protein encoded by the GRN gene. Mutations in the GRN gene leading to PGRN deficiency are associated with lysosomal storage diseases and various neurodegenerative diseases. Despite the significance of GRN function, the specific impact of GRN-/- condition on diverse biomolecules such as proteins, lipids, and metabolites remain unclear. This study employs a multi-omics approach, integrating proteomics, lipidomics, and metabolomics analyses for comprehensively unraveling the molecular alterations by GRN-/- condition. Proteins, lipids, and metabolites were obtained from the same sample using a single extraction method. Our result reveals distinct molecular profiles between iPSC and neurons, emphasizing upregulated synaptic proteins such as SYN1, SYT1, VAMP2, and SV2A in proteomics, decreased cardiolipin (CL) containing 16:0 and 18:1 acyl chain in lipidomics, and shifts in acetylcholine and amino acid in metabolomics. Furthermore, the GRN-/- condition induces significant alterations across the proteome, lipidome, and metabolome of induced pluripotent stem cells (iPSC) and iPSC-derived neurons, unveiling unique metabolic pathways. Although this study was conducted at a whole cell level, this comprehensive perspective contributes to our understanding of the intricate interplay among proteins, lipids, and metabolites in neurodevelopment and neurodegenerative diseases.

2023-11-13 | MSV000093388 | GNPS

iPSC derived motor neuron cultures from C9ORF72 carriers

Project description:Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat–containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-?, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS. Transcriptome profiling from iPSC derived motor neurons compared to controls

2013-11-07 | E-GEOD-52202 | biostudies-arrayexpress

Quantified metabolomics and lipidomics profiles reveal serum metabolic alterations and distinguished metabolites of seven chronic metabolic diseases

Project description:Quantified metabolomics and lipidomics profiles reveal serum metabolic alterations and distinguished metabolites of seven chronic metabolic diseases

2024-01-11 | PXD048576 | iProX

Neuronal accumulation of peroxidated lipids promotes demyelination and neurodegeneration though the activation of the microglial NLRP3 inflammasome

Project description:Peroxidated lipids accumulate in the presence of reactive oxygen species and are linked to neurodegenerative diseases. Here we found that neuronal ablation of Arf1, a small GTPase important for lipid homeostasis, promoted the accumulation of peroxidated lipids, lipid droplets and ATP in the mouse brain and led to neuroinflammation, demyelination, and neurodegeneration, mainly in the spinal cord and hindbrain. Ablation of Arf1 in cultured primary neurons led to an increase in peroxidated lipids in co-cultured microglia, the activation of the microglial NLRP3 inflammasome, and the release of inflammatory cytokines in an APOE-dependent manner. Deleting the Nlrp3 gene rescued the neurodegenerative phenotypes in the neuronal Arf1-ablated mice. We also observed a reduction in Arf1 in human brain tissue from amyotrophic lateral sclerosis and multiple sclerosis patients. Together, our results uncover a previously unrecognized role of peroxidated lipids released from damaged neurons in the activation of a neurotoxic microglial NLRP3 pathway that may play a role in human neurodegeneration.

2021-09-08 | GSE183483 | GEO

Genome-wide CRISPRi/a screens in human neurons link lipid imbalance to ferroptosis

Project description:Neurons are unique among all human cell types in their high energy demand, long lifespans and rich lipid contents. As such, neurons exhibit unique vulnerability to oxidative stress caused by redox imbalance in aging and neurodegenerative diseases (NDDs). To systematically identify regulators of neuronal survival under oxidative stress and regulators of neuronal redox homeostasis, we conducted multiple survival- and FACS-based genome-wide screens in human iPSC-derived neurons, using our functional genomics toolkit including a previously established CRISPRi approach and a newly developed CRISPRa approach. So far, these are the first genome-wide screens in human neurons. Our results revealed that inhibiting glycosphingolipids (GSLs) degradation by depletion of prosaposin (PSAP) drives the formation of lipofuscins in neurons which leads to iron accumulation and strongly induces ROS production that oxidizing lipids and leads to neuronal ferroptosis under oxidative stress. We also conducted single cell CROP-seq screens that revealed transcriptomic signatures of NDD-associated genes. These datasets are freely available through our open-access database CRISPRbrain.

2020-06-23 | GSE152988 | GEO

iPSC derived motor neuron cultures from C9ORF72 carriers

Project description:Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat–containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-α, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS.

2013-11-07 | GSE52202 | GEO

Obatoclax rescues FUS-ALS phenotypes in iPSC-derived neurons by inducing autophagy

Project description:Disruption of protein homeostasis plays an essential role in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). One strategy for restoring protein homeostasis and protecting neurons is to de-repress autophagy by disrupting the inhibitory BECN1/BCL2 complex, which has been shown to improve healthspan and lifespan in mice. We screened small molecule BH3 mimetics using an induced pluripotent stem cell (iPSC)-based model of ALS with a FUS mutation and identified obatoclax rescued neurons at by reducing cytoplasmic FUS levels, restoring protein homeostasis, and reducing degeneration.

2023-10-16 | PXD042427 | Pride

Modeling spinocerebellar ataxias 2 and 3 with iPSCs reveals a major role of glutamate in disease pathology

Project description:Spinocerebellar ataxias 2 and 3 (SCA2 and SCA3) are dominantly inherited neurodegenerative diseases caused by expansion of polyglutamine-encoding CAG repeats in the affected genes. The etiology of these disorders is known to involve widespread loss of neuronal cells in the cerebellum, however, the mechanisms that contribute to cell death are still elusive. Here we established SCA2 and SCA3 induced pluripotent stem cells (iPSCs) and demonstrated that SCA-associated pathological features can be recapitulated in SCA-iPSC-derived neurons. Importantly, our results also revealed that glutamate stimulation promotes the development of disease-related phenotypes in SCA-iPSC-derived neurons, including altered composition of glutamatergic receptors, destabilized intracellular calcium, and eventual cell death. Furthermore, anti-glutamate drugs and calcium stabilizer treatment protected the SCA-iPSC-derived neurons and reduced cell death. Collectively, our study demonstrates that the SCA-iPSC-derived neurons can recapitulate SCA-associated pathological features, providing a valuable tool to explore SCA pathogenic mechanisms and screen drugs to identify potential SCA therapeutics.

2019-02-14 | GSE96826 | GEO

Identification of neurexophilin 3 as a novel maturation factor for induced pluripotent stem cell-derived dopaminergic neuron progenitors

Project description:To develop more potent cell transplantation therapy for neurodegenerative disorder such as Parkinson’s disease (PD), the condition of the host brain environment should be considered to improve the outcome of grafted neurons. However, we never know which condition of host brain environment is suitable and supportive for the donor cells. In addition, what endogenous factor(s) do contribute to improve the engraftment of donor cells in host brain? Therefore, the identification of such effective factor(s) strongly contribute to improve the overcome of cell transplantation therapy. Here, we constructed the experimental approach to identify the effective soluble factor(s) for cell-grafting by comparison between various parkinsonian mouse brain condition and transplantation outcome using induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neuron progenitors. According to our experimental approach, we have identified secreted peptide, neurexophilin 3 (NXPH3) that enhance the survival of grafted-iPSC-derived DA neurons. Grafted-iPSC-derived DA neurons were increased by local supplement of NXPH3 protein. In addition, the expression level of NXPH3 in putamen of PD patients was significantly decreased than that of normal controls by using postmortem samples. These findings would be expected to contribute the new experimental strategy to indentify the endogenous effective factors for cell-grafting as in vivo application of stem cell technology.

2015-06-12 | GSE60080 | GEO

An integrated metabolomics and lipidomics approach for the study of metabolic network and early diagnosis in cerebral infarction

Project description:Cerebral infarction (CI) remains a major cause of high mortality and long-term disability worldwide. The exploration of biomarkers and pathogenesis is crucial for early diagnosis of CI. Although the understanding of metabolic perturbations underlying CI has increased in recent years, the relationship between altered metabolites and disease pathogenesis has only been partially elucidated and requires further investigation. Here, we performed an integrated metabolomics and lipidomics analysis on 59 healthy subjects and 47 CI patients. Ultimately, 49 metabolites and 68 lipids biomarkers were identified and enriched in 24 disturbed pathways. The metabolic network revealed a significant interaction between altered lipids and other metabolites. Using ROC analysis, a panel of 3 polar metabolites and 7 lipids was optimized in training set, which was taurine, oleoylcarnitine, creatinine, PE(22:6/P-18:0), Cer 34:2, GlcCer(d18:0/18:0), DG 44:0, LysoPC(16:0), 22:6-OH/LysoPC and TAG58:7-FA22:4. Subsequently, a support vector machine (SVM) model was constructed and validated, which showed an excellent predictive ability in validation set. Thereby, the integrated metabolomics and lipidomics approach could contribute to a comprehensive understanding of the metabolic dyshomeostasis associated with the pathogenesis underlying CI. The present research may promote a deeper understanding and early diagnosis of CI in clinic.

2023-03-11 | PXD036199 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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