Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Derivation of sensory neurons from iPSCs.

ABSTRACT: Characterization of the gene expression changes accompanying the differentiation of hPSC-sensory from embryonic stem cells through to neuronal precursor cells. We also compare the time course gene expression profile to that of the relevant primary human tissue, human dorsal root ganglia (hDRG). A reference brain sample is also included.

ORGANISM(S): Homo sapiens

SUBMITTER: Alex Gutteridge

PROVIDER: E-MTAB-3031 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

Young Gareth T GT Gutteridge Alex A Fox Heather DE H Wilbrey Anna L AL Cao Lishuang L Cho Lily T LT Brown Adam R AR Benn Caroline L CL Kammonen Laura R LR Friedman Julia H JH Bictash Magda M Whiting Paul P Bilsland James G JG Stevens Edward B EB

Molecular therapy : the journal of the American Society of Gene Therapy 20140515 8

The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. W ...[more]

PMID: 24832007

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Project description:Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9 M-BM-5M or 0 to 40M-BM-5g/dl) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural precursor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9 M-BM-5M or 40M-BM-5g/dl Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChipM-BM-. demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development. We analyzed the methylation profile of undifferentiated (n=2 independent experiments) and differentiating (n=2 independent experiments) human embryonic stem cells (hESCs) acutely exposed to losed to lead (Pb) and neural precursor cells derived from hESCs chronically exposed to Pb throughout the neural differentiation process (n=3 independent experiments).

Dataset Information

Derivation of sensory neurons from iPSCs.

Publications

Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

Similar Datasets

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