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Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje n...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043485/ https://www.ncbi.nlm.nih.gov/pubmed/24893313 http://dx.doi.org/10.1371/journal.pbio.1001874 |
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author | Ridder, Kirsten Keller, Sascha Dams, Maria Rupp, Anne-Kathleen Schlaudraff, Jessica Del Turco, Domenico Starmann, Julia Macas, Jadranka Karpova, Darja Devraj, Kavi Depboylu, Candan Landfried, Britta Arnold, Bernd Plate, Karl H. Höglinger, Günter Sültmann, Holger Altevogt, Peter Momma, Stefan |
author_facet | Ridder, Kirsten Keller, Sascha Dams, Maria Rupp, Anne-Kathleen Schlaudraff, Jessica Del Turco, Domenico Starmann, Julia Macas, Jadranka Karpova, Darja Devraj, Kavi Depboylu, Candan Landfried, Britta Arnold, Bernd Plate, Karl H. Höglinger, Günter Sültmann, Holger Altevogt, Peter Momma, Stefan |
author_sort | Ridder, Kirsten |
collection | PubMed |
description | Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation. |
format | Online Article Text |
id | pubmed-4043485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40434852014-06-09 Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation Ridder, Kirsten Keller, Sascha Dams, Maria Rupp, Anne-Kathleen Schlaudraff, Jessica Del Turco, Domenico Starmann, Julia Macas, Jadranka Karpova, Darja Devraj, Kavi Depboylu, Candan Landfried, Britta Arnold, Bernd Plate, Karl H. Höglinger, Günter Sültmann, Holger Altevogt, Peter Momma, Stefan PLoS Biol Research Article Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation. Public Library of Science 2014-06-03 /pmc/articles/PMC4043485/ /pubmed/24893313 http://dx.doi.org/10.1371/journal.pbio.1001874 Text en © 2014 Ridder et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ridder, Kirsten Keller, Sascha Dams, Maria Rupp, Anne-Kathleen Schlaudraff, Jessica Del Turco, Domenico Starmann, Julia Macas, Jadranka Karpova, Darja Devraj, Kavi Depboylu, Candan Landfried, Britta Arnold, Bernd Plate, Karl H. Höglinger, Günter Sültmann, Holger Altevogt, Peter Momma, Stefan Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title | Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title_full | Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title_fullStr | Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title_full_unstemmed | Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title_short | Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation |
title_sort | extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043485/ https://www.ncbi.nlm.nih.gov/pubmed/24893313 http://dx.doi.org/10.1371/journal.pbio.1001874 |
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