Primary human erythroid progenitor cells HDAC1 and HDAC2 shRNA knockdown samples
Transcriptomics Dataset
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General Information
AccessionGSE22366
TitlePrimary human erythroid progenitor cells HDAC1 and HDAC2 shRNA knockdown samples
DescriptionGene expression profiling was performed on primary human erythroid progenitor cells expressing a control shRNA (luciferase), two different HDAC1 shRNAs, and two different HDAC2 shRNAs. The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a novel bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22366
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Keyword
Dataset Accession

Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset

Dataset Accession
Tool Name
Direction
Hs Gene Symbol
Mm Gene Symbol
Geneset

Small molecules which mimic HDAC1 KD
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse HDAC1 KD
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic HDAC1 KD
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse HDAC1 KD
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic HDAC2 KD
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse HDAC2 KD
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in HDAC1 KD
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in HDAC1 KD
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in HDAC2 KD
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in HDAC1 KD
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
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