Abstract
We report on a forward RNAi screen in primary human hematopoietic stem and progenitor cells, using pooled lentiviral shRNA libraries deconvoluted by next generation sequencing. We identify MAPK14/p38α as a modulator of ex vivo stem cell proliferation and show that pharmacologic inhibition of p38 dramatically enhances the stem cell activity of cultured umbilical cord blood derived hematopoietic cells. p38 inhibitors should thus be considered in strategies aiming at expanding stem cells for clinical benefit.
Publication types
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Evaluation Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation / drug effects*
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Cells, Cultured
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Drug Discovery
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Hematopoietic Stem Cells / drug effects*
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / physiology
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High-Throughput Screening Assays
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Humans
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Mice, Transgenic
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Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 14 / genetics
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Mitogen-Activated Protein Kinase 14 / physiology*
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Molecular Targeted Therapy
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RNA Interference* / physiology
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RNA, Small Interfering / isolation & purification
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RNA, Small Interfering / pharmacology*
Substances
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RNA, Small Interfering
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Mitogen-Activated Protein Kinase 14