Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder.
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.
O'Connell
Ryan M
RM
Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Rao
Dinesh S
DS
Chaudhuri
Aadel A
AA
Boldin
Mark P
MP
Taganov
Konstantin D
KD
Nicoll
John
J
Paquette
Ronald L
RL
Baltimore
David
D
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
D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; C524942:MIRN155 microRNA, human; D035683:MicroRNAs