Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA136445 | ENA |
REPOSITORIES: ENA
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Project description:We developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons.
2017-01-31 | GSE89503 | GEO
Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors, early neurons, and brain organoids. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis. Multiple dysregulated proteins were found in pathways related to synapses, in line with postmortem tissue studies of schizophrenia patients. However, organoids and immature neurons exhibit impairments in pathways never before found in patient-derived induced pluripotent stem cell studies, such as spliceosomes and amino acid metabolism. In conclusion, here we provide comprehensive, large-scale, protein-level data that may uncover underlying mechanisms of the developmental origins of schizophrenia.
2023-03-11 | PXD026381 | Pride
Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors, early neurons, and brain organoids. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis. Multiple dysregulated proteins were found in pathways related to synapses, in line with postmortem tissue studies of schizophrenia patients. However, organoids and immature neurons exhibit impairments in pathways never before found in patient-derived induced pluripotent stem cell studies, such as spliceosomes and amino acid metabolism. In conclusion, here we provide comprehensive, large-scale, protein-level data that may uncover underlying mechanisms of the developmental origins of schizophrenia.
2023-03-11 | PXD026593 | Pride
Project description:As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients. Total RNAs were isolated from both iPS cells and differentiating neurons, and the sequenced material was pre-amplified using the NuGen Ovation amplification system. RNA-Seq libraries were prepared and carried out on Illumina HiSeq200.
2011-10-06 | E-GEOD-32625 | biostudies-arrayexpress
Project description:Induced pluripotent stem cell (iPSC) technology presents a unique opportunity to model schizophrenia (SCZ) and other neuropsychiatric disorders in vitro by providing investigators with the means to grow patient-specific neurons. Three approaches are possible regarding disease modeling for a genetically heterogenous disorder, like SCZ. One is the draw subjects from the general patient population who have suspected but undefined disease-causing genetic variants. Another is to focus on a common phenotype, such as clinical presentation, response to medications or age of onset. The third is to use patients who have on a common genetic etiology. We have chosen the latter approach and are developing a library of iPSCs from patients with SCZ who harbor chromosome 22q11.2 microdeletions. In this preliminary study involving 4 patients and 4 controls, gene expression profiling was carried out on early differentiating neurons using RNA-seq. Several important observations were made. First, despite the dramatic molecular changes that occur during the reprogramming of a somatic cell into an iPSC, and its subsequent differentiation into neurons, processes that require months of cultivation with multiple changes in growth medium and treatment with a variety of growth factors, we show that 22q11.2 haploinsufficiency at the DNA level is recapitulated in vitro by substantial decreases in the expression of nearly every gene in the deleted region. Overall, transcriptome profiling revealed significant changes in the expression of 604 genes (423 increased in the SCZ samples, 181 decreased; >1.5-fold change, uncorrected p<0.05). Among the differentially expressed genes were a number of SCZ candidates and genes involved in retinoic acid (RA) signaling. In addition, there was some overlap with the differentially expressed genes found in another study using SCZ patients who do not have 22q11.2 del, one of which was CYP26A1, which codes for one of the major enzymes involved in RA metabolism. Although the sample size in this preliminary study is small, the findings support the idea that dysregulated RA-signaling could be a potential target for therapeutic intervention in SZ associated with 22q11.2 del, and perhaps other subgroups of patients. 4 controls and 4 patients
2013-11-01 | E-GEOD-46562 | biostudies-arrayexpress
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:As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.
2011-10-06 | GSE32625 | GEO
Project description:To identify morphological and functional phenotypes relevant for SCZ, we generated iPSC-derived dopaminergic neurons from three healthy controls and four patient with schizophrenia. We then performed gene expression profiling analysis using data obtained from RNA-seq of four schizophrenia patients and three controls to determine significantly deregulated genes in schizophrenia dopaminergic neurons.
2024-08-27 | GSE275064 | GEO
Project description:clozapine and schizophrenia patient-derived neurons
| PRJEB50039 | ENA