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Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder

O'Connell, Ryan M. and Rao, Dinesh S. and Chaudhuri, Aadel A. and Boldin, Mark P. and Taganov, Konstantin D. and Nicoll, John and Paquette, Ronald L. and Baltimore, David (2008) Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. Journal of Experimental Medicine, 205 (3). pp. 585-594. ISSN 0022-1007. PMCID PMC2275382. https://resolver.caltech.edu/CaltechAUTHORS:OCOjem08

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Image (JPEG) (Figure S1. Mature cell–depleted bone marrow populations up-regulate miR-155 to higher levels in response to LPS than mature cell–enriched populations) - Supplemental Material
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Image (JPEG) (Figure S2. Bone marrow cell dynamics after 24 h of LPS treatment) - Supplemental Material
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Image (JPEG) (Figure S3. Coexpression of GFP and miR-155 in several lymphoid organs) - Supplemental Material
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Image (JPEG) (Figure S4. Comparative expression of miR-155 induced by LPS or produced from MSCV-155 in myeloid cells) - Supplemental Material
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Image (JPEG) (Figure S5. miR-155 target identification and analysis scheme) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1084/jem.20072108DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2275382/PubMed CentralArticle
ORCID:
AuthorORCID
Rao, Dinesh S.0000-0002-0794-9337
Boldin, Mark P.0000-0003-4593-0669
Baltimore, David0000-0001-8723-8190
Additional Information:© 2008, The Rockefeller University Press. Submitted: 1 October 2007. Accepted: 25 January 2008. Published online 25 February 2008. We thank Jose Luis Riechmann, Vijaya Rao, Jaclyn Shingara, and David Brown for help with microarray work. R.M. O'Connell was funded by the Irvington Institute Fellowship Program of the Cancer Research Institute. D.S. Rao was funded by the American Society of Hematology Basic Science Fellow Scholar Award. A.A. Chaudhuri was funded by the Howard Hughes Medical Institute's Medical Research Training Fellow Award. Part of this work was also funded by National Institutes of Health (NIH) grants. This work was supported by the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology and by NIH Grants. D. Baltimore is a scientific advisor to Regulus, a company devoted to microRNA therapeutics. All other authors have no conflicting financial interests.
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
Funders:
Funding AgencyGrant Number
Cancer Research InstituteUNSPECIFIED
American Society of HematologyUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHUNSPECIFIED
Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC2275382
Record Number:CaltechAUTHORS:OCOjem08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:OCOjem08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9851
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:24 Mar 2008
Last Modified:16 Apr 2020 22:52

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