Transcriptomics

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Gene expression profiling coupled with the Connectivity Map database-mining reveals potential therapeutic drugs for Hirschsprung disease


ABSTRACT: Hirschsprung disease (HD) is a congenital intestinal anomaly, which derives from a failure to form enteric ganglia in the lower bowel. Surgery is a major therapeutic strategy and neural stem cells transplantation is believed as a promising approach. However, we still face many challenges. To better characterize the pathology of HD, we used Agilent microarrays to analyze the gene expression profiles of surgically resected bowel tissue from 8 HD patients and 8 controls. A total of 253 genes were differentially expressed between the two groups using SAM software with threshold set at fold-change >2.0 and q-value <0.05. Gene Ontology analysis demonstrated that genes related to regulation of neuron development were significantly enriched. Differentially expressed genes (DEGs) involved in neuron development were further validated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Moreover, in an attempt to seek potential drugs for HD, we correlated the observed gene expression patterns in HD to those of small molecule compounds via the Connectivity Map (cMap) database. Several compounds were screened that could rescue the dysregulated molecular signature in HD, proposing a testable hypothesis about possible therapeutic agents as a novel remedy for HD. In conclusion, our work may enhance our understanding the molecular changes in HD. More importantly, this study opens new fields of investigation into pharmacological intervention for HD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98502 | GEO | 2018/06/01

REPOSITORIES: GEO

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