title: RNA interference screening to detect targetable molecules in hematopoietic stem cells.
abstract: OBJECTIVE
  The molecular principles regulating hematopoietic stem cells (HSCs) remain incompletely defined. In this review, we will discuss how RNA interference (RNAi) screening has emerged as a new and powerful tool to molecularly dissect various functional aspects of both normal and malignant HSCs, and how this may ultimately enable the discovery of novel therapeutic targets for clinical applications.
  
  
  RESULTS
  Advances in RNAi technology and the creation of short hairpin RNA retroviral and lentiviral vector-libraries have provided tools to perform broad forward genetic screens in primary mammalian hematopoietic cells. Recent studies have identified novel fate determinants in murine HSCs as well as potential targets for ex-vivo expansion of human HSCs. RNAi screens have further unraveled tumor suppressor genes associated with hematopoietic neoplasms as well as candidate therapeutic targets in leukemic cells.
  
  
  CONCLUSIONS
  RNAi screening is a feasible tool to discover novel molecules that regulate both normal and malignant HSCs, thus increasing our general understanding of the physiology and pathophysiology of hematopoiesis. Moreover, RNAi technology holds great promise for the discovery of specific targets for therapeutic interventions.
authors.affiliation: Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden *Christine Karlsson and Justyna Rak contributed equally to the writing of this article and are considered co-first authors.
authors.forename: Christine
authors.initials: C
authors.lastname: Karlsson
authors.forename: Justyna
authors.initials: J
authors.lastname: Rak
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D051379:Mice; D058990:Molecular Targeted Therapy; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering