Single-cell RNA sequencing data from hiPSC disease modeling of Loeys-Dietz Syndrome (LDS)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA733141 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:For in vitro disease modeling of LDS, we used healthy donor cells (TGFBR1+/+), and generated heterozygote (TGFBR1A230T/+), and homozygote (TGFBR1A230T/A230T) knock-in clones using CRISPR-Cas9 gene editing. We also generated hiPSC from peripheral blood mononuclear cells harvested from an LDS patient, and corrected the mutation in the patient-derived hiPSC. To address the lineage-specific effects of TGFBR1A230T, and SMAD3c.652delA/+, hiPSC were differentiated into cardiovascular progenitor cell-derived smooth muscle cells (CPC-SMC), and neural crest stem cell-derived smooth muscle cells (NCSC-SMC) using in vitro differentiation protocols. We performed large-scale single cell profiling of the resulting CPC-SMC and NCSC-SMC.
2021-08-04 | GSE175647 | GEO
Project description:Cornelia de Lange syndrome (CdLS) is an autosomal dominant disease mainly caused by mutations in the Nipped-B-like protein (NIPBL) gene resulting in the alteration of the cohesin pathway. Here, we generated human induced pluripotent stem cells (hiPSCs) from a CdLS patient carrying a mutation in the NIPBL gene, c.5483G>A, and tested CRISPR-Cas based approaches to repair the genetic defect. We applied an efficient and precise method of gene correction through CRISPR-Cas induced homology directed repair (HDR), which allowed the generation of hiPSC clones with regular karyotype and preserved stemness. The efficient and precise gene replacement strategy developed in this study can be extended to the modification of other genomic loci in hiPSCs. Isogenic wild-type and mutated hiPSCs produced with the CRISPR-Cas technology are fundamental CdLS cellular models to study the disease molecular determinants and identifying therapeutic targets.
2023-03-17 | E-MTAB-11604 | biostudies-arrayexpress
Project description:Trans-differentiation of human induced pluripotent stem cells into neurons (hiPSC-N) via Ngn2-induction has become an efficient system to quickly generate neurons for disease modeling and in vitro assay development, a significant step up from previously used neoplastic and other cell lines. Recent single-cell interrogation of Ngn2-induced neurons however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. Here we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days) and of hiPSC-N / hiPSC-A co-culture. We explore how often genes differentially expressed between conditions relate to genetic risk for neuropsychiatric disease. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. Both show heterogeneity and share similarity with multiple in vivo cell fates, and both cell types more precisely approximate their in vivo counterparts when co-cultured. hiPSC-A show more heterogeneity and similarities to other non-neural cell types, especially when cultured in isolation. Gene expression data from the hiPSC-N show excess of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, which together with our observation of similarities with in vivo neurons earlier in development suggest they may be a better model for neurodevelopmental disorders. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAl2022 .
2024-03-04 | GSE260498 | GEO
Project description:Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) sets their identity back to an embryonic age. This presents a fundamental hurdle for modeling late-onset disorders using iPSC-derived cells. We therefore developed a strategy to induce age-like features in multiple iPSC-derived lineages and tested its impact on modeling Parkinson’s disease (PD). We first describe markers that predict fibroblast donor age and observed the loss of these age-related markers following iPSC induction and re-differentiation into fibroblasts. Remarkably, age-related markers were readily induced in iPSC-derived fibroblasts or neurons following exposure to progerin including dopamine neuron-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes requiring both aging and genetic susceptibility such as frank dendrite degeneration, progressive loss of tyrosine-hydroxylase expression and enlarged mitochondria or Lewy body-precursor inclusions. Our study presents a strategy for inducing age-related cellular properties and enables the modeling of late-onset disease features. Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.
2014-01-23 | E-GEOD-52431 | biostudies-arrayexpress
Project description:Despite its clear impact on Alzheimer’s Disease (AD) risk, apolipoprotein (apo) E4’s contributions to AD etiology remain poorly understood. Progress in answering this and other questions in AD research has been limited by an inability to model human-specific phenotypes in an in vivo environment. Here we transplanted human induced pluripotent stem cell (hiPSC)-derived neurons carrying normal apoE3 or pathogenic apoE4 into human apoE3 or apoE4 knock-in mouse hippocampi, enabling us to disentangle the effects of apoE4 produced in human neurons and in the brain environment. Using single nucleus RNA-sequencing (snRNA-seq), we identified key transcriptional changes specific to human neuron subtypes in response to endogenous or exogenous apoE4. We also found that Aβ from transplanted human neurons formed plaque-like aggregates, with differences in localization and interaction with microglia depending on the transplant and host apoE genotype. These findings highlight the power of in vivo chimeric disease modeling for studying AD.
2020-06-20 | GSE152867 | GEO
Project description:Schizophrenia is a debilitating neurological disorder for which no cure exists. Few defining characteristics of schizophrenic neurons have been identified and the molecular mechanisms responsible for schizophrenia are not well understood, in part due to the lack of patient material for study. Human induced pluripotent stem cells (hiPSCs) offer a new strategy for studying schizophrenia. We have created the first cell-based human model of a complex genetic psychiatric disease by generating hiPSCs from schizophrenic patients and subsequently differentiating these cells to hiPSC-derived neurons in vitro. Schizophrenic hiPSC-derived neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of schizophrenic hiPSC-derived neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the schizophrenic phenotype were ameliorated following treatment of schizophrenic hiPSC-derived neurons with the antipsychotic loxapine. 3 independent differentiations (biological replicates) for each of four control and four schizophrenic patients were analyzed.
2011-05-01 | E-GEOD-25673 | biostudies-arrayexpress
Project description:Proteomic analysis of hiPSC-CMs with drug treatment
2021-05-01 | MSV000087351 | MassIVE
Project description:DG accounts for most of the identifiable cases of TOF. Exploring and comparing the transcriptome of hiPSC-CMs and hiPSC-CPs from TOF-DG and TOF-ND could provide a bettering understanding on TOF.
2023-08-29 | GSE186293 | GEO
Project description:Target-agnostic discovery of Rett Syndrome therapeutics by coupling computational network analysis and CRISPR-enabled in vivo disease modeling
| PRJNA818187 | ENA
Project description:Modeling Down syndrome AML by introducing disese-specific mutations in iPSCs
| PRJNA779425 | ENA