title: Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder.
abstract: Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155-induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
authors.affiliation: Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Rao
authors.forename: Aadel A
authors.initials: AA
authors.lastname: Chaudhuri
authors.forename: Mark P
authors.initials: MP
authors.lastname: Boldin
authors.forename: Konstantin D
authors.initials: KD
authors.lastname: Taganov
authors.forename: John
authors.initials: J
authors.lastname: Nicoll
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Paquette
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; C524942:MIRN155 microRNA, human; D035683:MicroRNAs