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| Status |
Public on Jun 28, 2010 |
| Title |
Primary human erythroid progenitor cells HDAC1 and HDAC2 shRNA knockdown samples |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Gene 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.
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| Overall design |
Gene expression profiling was performed on primary human erythroid progenitor cells expressing a control shRNA (luciferase, n=3), two different HDAC1 shRNAs (n=2 and n=3), and two different HDAC2 shRNAs (n=3 for each).
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| Contributor(s) |
Ebert BL, Bradner JE, Ross KN |
| Citation(s) |
20616024 |
| Submission date |
Jun 15, 2010 |
| Last update date |
Jan 17, 2017 |
| Contact name |
Benjamin L Ebert |
| E-mail(s) |
Benjamin_Ebert@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Street address |
Harvard Medical School
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL3921 |
[HT_HG-U133A] Affymetrix HT Human Genome U133A Array |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE22369 |
HDAC1 and HDAC2 in fetal hemoglobin induction |
|
| Relations |
| BioProject |
PRJNA129225 |
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