title: RNAi screen identifies MAPK14 as a druggable suppressor of human hematopoietic stem cell expansion.
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.
authors.affiliation: Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Baudet
authors.forename: Christine
authors.initials: C
authors.lastname: Karlsson
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Safaee Talkhoncheh
authors.forename: Roman
authors.initials: R
authors.lastname: Galeev
authors.forename: Mattias
authors.initials: M
authors.lastname: Magnusson
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D055808:Drug Discovery; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D058990:Molecular Targeted Therapy; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; D048308:Mitogen-Activated Protein Kinase 14