The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment
| Autor: | Rustam R. Mundegar, Ralf B. Schäfer, Ulrich Knauf, Viktor Janzen, Stefan Garbe, Margit Zweyer, Anton Wernig, Marius Wernig, Thomas Franz, Gerlinde Wernig, Oliver Hoegemeier, Sebastian Stier |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Nuclear Transfer Techniques Time Factors Cellular differentiation Transgene Muscle Fibers Skeletal Cobra Cardiotoxin Proteins Bone Marrow Cells Muscle Development Phenylbutyrate Dystrophin Mice Cardiotoxin Genes Reporter medicine Animals Gene Silencing Transgenes Actin Bone Marrow Transplantation Multidisciplinary biology Cell Differentiation Biological Sciences Molecular biology Actins Chromatin Cell biology medicine.anatomical_structure biology.protein Mice Inbred mdx Female Bone marrow |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(33) |
| ISSN: | 0027-8424 |
| Popis: | Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of “revertant” fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the β-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of “silent” nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels. |
| Databáze: | OpenAIRE |
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