MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice
Abstract
During inflammation and infection, hematopoietic stem and progenitor cells are stimulated to proliferate and differentiate into mature immune cells, especially of the myeloid lineage. MicroRNA-146a (miR-146a) is a critical negative regulator of inflammation. Deletion of miR-146a produces effects that appear as dysregulated inflammatory hematopoiesis, leading to a decline in the number and quality of hematopoietic stem cells (HSCs), excessive myeloproliferation, and, ultimately, to HSC exhaustion and hematopoietic neoplasms. At the cellular level, the defects are attributable to both an intrinsic problem in the miR-146a–deficient HSCs and extrinsic effects of lymphocytes and nonhematopoietic cells. At the molecular level, this involves a molecular axis consisting of miR-146a, signaling protein TRAF6, transcriptional factor NF-κB, and cytokine IL-6. This study has identified miR-146a to be a critical regulator of HSC homeostasis during chronic inflammation in mice and provided a molecular connection between chronic inflammation and the development of bone marrow failure and myeloproliferative neoplasms.
Additional Information
© 2013 Zhao et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 10 January 2013; Accepted: 16 April 2013; Published: 21 May 2013. Author contributions: JLZ, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article, Contributed unpublished essential data or reagents; DSR, RMO, Conception and design, Acquisition of data, Analysis and interpretation of data; YG-F, Conception and design, Acquisition of data; DB, Conception and design, Analysis and interpretation of data, Drafting or revising the article. Ethics: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animal experiments were approved by the institutional animal care and use committee (IACUC) of the California Institute of Technology under protocol #1558.Attached Files
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Additional details
- PMCID
- PMC3660742
- Eprint ID
- 38606
- Resolver ID
- CaltechAUTHORS:20130521-130754509
- R01AI079243
- National Institute of Allergy and Infectious Diseases
- F30HL110691
- National Heart, Lung, and Blood Institute
- K08CA133521
- National Cancer Institute
- R00HL102228
- National Heart, Lung, and Blood Institute
- Created
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2013-05-23Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field