Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human embryonic stem cells and neuroepithelial cells

ABSTRACT: Comparing gene expressing profile of human embryonic stem cells and neuroepithelial cells differentiated from human embryonic stem cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Su-Chun Zhang

PROVIDER: E-MEXP-2426 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells.

Li Xue-Jun XJ Zhang Xiaoqing X Johnson M Austin MA Wang Zhi-Bo ZB Lavaute Timothy T Zhang Su-Chun SC

Development (Cambridge, England) 20091201 23

The directed differentiation of forebrain neuronal types from human embryonic stem cells (hESCs) has not been achieved. Here, we show that hESCs differentiate to telencephalic progenitors with a predominantly dorsal identity in a chemically defined medium without known morphogens. This is attributed to endogenous Wnt signaling, which upregulates the truncated form of GLI3, a repressor of sonic hedgehog (SHH). A high concentration of SHH, or the inhibition of Wnt by dickkopf 1 (DKK1) together wit ...[more]

PMID: 19906872

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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

Transcription profiling of human embryonic stem cells and neuroepithelial cells

Publications

Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells.

Similar Datasets

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