MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice
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 tha...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2013-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00537 |
| _version_ | 1811180635629289472 |
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| author | Jimmy L Zhao Dinesh S Rao Ryan M O’Connell Yvette Garcia-Flores David Baltimore |
| author_facet | Jimmy L Zhao Dinesh S Rao Ryan M O’Connell Yvette Garcia-Flores David Baltimore |
| author_sort | Jimmy L Zhao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:06:29Z |
| format | Article |
| id | doaj.art-bb1ca122fc784a52b8f89a38fa3a1437 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:29Z |
| publishDate | 2013-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bb1ca122fc784a52b8f89a38fa3a14372022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2013-05-01210.7554/eLife.00537MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in miceJimmy L Zhao0Dinesh S Rao1Ryan M O’Connell2Yvette Garcia-Flores3David Baltimore4Department of Biology, California Institute of Technology, Pasadena, United StatesDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Pathology, University of Utah, Salt Lake City, United StatesDepartment of Biology, California Institute of Technology, Pasadena, United StatesDepartment of Biology, California Institute of Technology, Pasadena, United StatesDuring 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.https://elifesciences.org/articles/00537hematopoiesisinflammationmicroRNAHSCcancerNF-kappaB |
| spellingShingle | Jimmy L Zhao Dinesh S Rao Ryan M O’Connell Yvette Garcia-Flores David Baltimore MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice eLife hematopoiesis inflammation microRNA HSC cancer NF-kappaB |
| title | MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| title_full | MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| title_fullStr | MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| title_full_unstemmed | MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| title_short | MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| title_sort | microrna 146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice |
| topic | hematopoiesis inflammation microRNA HSC cancer NF-kappaB |
| url | https://elifesciences.org/articles/00537 |
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