Functional maturation of human iPSC-derived pyramidal neurons in vivo is dependent on proximity with the host tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246427 | GEO | 2023/11/01
REPOSITORIES: GEO
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Project description:Human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for characterising mid-brain dopaminergic neurons. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets. A mature physiological cellular model of human dopaminergic neurons. human iPSc lines were derived from normal human dermal fibroblasts.
2013-01-31 | E-GEOD-43903 | biostudies-arrayexpress
Project description:Human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for characterising mid-brain dopaminergic neurons. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets. A mature physiological cellular model of human dopaminergic neurons. human iPSc lines were derived from normal human dermal fibroblasts.
2013-01-31 | E-GEOD-43902 | biostudies-arrayexpress
Project description:We have generated human induced Pluripotent Stem cells (hiPSc) using Sendai virus-mediated delivery of reprogramming factors. hiPSc lines have been screened using SNP array to assess chromosomal stability (alongside the fibroblast lines from which they derived), and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets, prior to differentiation and downstream assays. Single cell RT-qPCR analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity. Handel AE, Chintawar S, Lalic T, Whiteley E, Giustacchini A, Argoud K, Sopp P, Bowden R, Cowley SA, Newey S, Ackerman C, Ponting CP and Cader ZM. Submitted human iPSc lines were derived from human dermal fibroblasts from control donors. SNP and gene expression datasets from control lines. Note that iPS NHDF-1, also used in the current study, has been published previously [Van Wilgenburg B., Browne C., Vowles J. & Cowley S. A. Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PLoS One 8, e71098 (2013); Physiological characterisation of human iPS-derived dopaminergic neurons. Hartfield EM, Yamasaki-Mann M, Ribeiro Fernandes HJ, Vowles J, James WS, Cowley SA, Wade-Martins R. PLoS One. 2014 9(2):e87388]
2015-05-28 | E-GEOD-69287 | biostudies-arrayexpress
Project description:We have generated human induced Pluripotent Stem cells (hiPSc) using Sendai virus-mediated delivery of reprogramming factors. hiPSc lines have been screened using SNP array to assess chromosomal stability (alongside the fibroblast lines from which they derived), and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets, prior to differentiation and downstream assays. Single cell RT-qPCR analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity. Handel AE, Chintawar S, Lalic T, Whiteley E, Giustacchini A, Argoud K, Sopp P, Bowden R, Cowley SA, Newey S, Ackerman C, Ponting CP and Cader ZM. Submitted human iPSc lines were derived from human dermal fibroblasts from control donors. SNP and gene expression datasets from control lines. Note that iPS NHDF-1, also used in the current study, has been published previously [Van Wilgenburg B., Browne C., Vowles J. & Cowley S. A. Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PLoS One 8, e71098 (2013); Physiological characterisation of human iPS-derived dopaminergic neurons. Hartfield EM, Yamasaki-Mann M, Ribeiro Fernandes HJ, Vowles J, James WS, Cowley SA, Wade-Martins R. PLoS One. 2014 9(2):e87388]
2015-05-28 | E-GEOD-69288 | biostudies-arrayexpress
Project description:Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80–85%1. Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue2 and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD3, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder. 4 samples/no replicates/genotyped for copy number variation, using the same refrence sample on nimblegen's 080131_HG18_WG_CGH_v2DCR_HX1 design, a dual color microarry, 2.1 million probes platform.
2011-08-12 | E-GEOD-30737 | biostudies-arrayexpress
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia (SCZD) generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SCZD might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SCZD patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SCZD hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes, reduced WNT signaling and aberrant cellular migration. 3 independent differentiations (biological replicates) for each of four control and four schizophrenic patients were analyzed.
2014-04-01 | E-GEOD-40102 | biostudies-arrayexpress
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the âageâ of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.
2016-03-14 | E-GEOD-63738 | biostudies-arrayexpress
Project description:Human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for characterising mid-brain dopaminergic neurons. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets. A mature physiological cellular model of human dopaminergic neurons.
2013-01-31 | GSE43903 | GEO
Project description:Human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for characterising mid-brain dopaminergic neurons. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets. A mature physiological cellular model of human dopaminergic neurons.
2013-01-31 | GSE43902 | GEO
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus. We directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into forebrain neurons. SZ hiPSC differentiated into forebrain neurons have altered expression of a number of synaptic genes. Methods: We compared global transcription of forebrain neurons from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC neuron samples; 107 genes were significantly differentially expressed (FDR<0.01)
2016-04-21 | GSE63734 | GEO