Pluripotency associated genes are reactivated by chromatin-modifying agents in neurosphere cells
| Autor: | Roberto Ensenat‐Waser, Timo C. Dinger, Alexandra Rolletschek, Anna M. Wobus, Duttu S. Vallabhapurapu, Thomas Hieronymus, Martin Zenke, David Ruau, Christine Hacker, Albrecht M. Müller |
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| Rok vydání: | 2008 |
| Předmět: |
Homeobox protein NANOG
Pluripotent Stem Cells Mice Transgenic Biology Hydroxamic Acids Kruppel-Like Factor 4 Mice Prosencephalon SOX2 Neurosphere medicine Animals Humans Cells Cultured Regulation of gene expression Neurons Gene Expression Regulation Developmental Cell Biology Molecular biology Chromatin Mice Inbred C57BL Trichostatin A DNA methylation Molecular Medicine sense organs Stem cell Developmental Biology medicine.drug |
| Zdroj: | Stem cells (Dayton, Ohio). 26(4) |
| ISSN: | 1549-4918 |
| Popis: | Chromatin architecture in stem cells determines the pattern of gene expression and thereby cell identity and fate. The chromatin-modifying agents trichostatin A (TSA) and 5-Aza-2′-deoxycytidine (AzaC) affect histone acetylation and DNA methylation, respectively, and thereby influence chromatin structure and gene expression. In our previous work, we demonstrated that TSA/AzaC treatment of neurosphere cells induces hematopoietic activity in vivo that is long-term, multilineage, and transplantable. Here, we have analyzed the TSA/AzaC-induced changes in gene expression by global gene expression profiling. TSA/AzaC caused both up- and downregulation of genes, without increasing the total number of expressed genes. Chromosome analysis showed no hot spot of TSA/AzaC impact on a particular chromosome or chromosomal region. Hierarchical cluster analysis revealed common gene expression patterns among neurosphere cells treated with TSA/AzaC, embryonic stem (ES) cells, and hematopoietic stem cells. Furthermore, our analysis identified several stem cell genes and pluripotency-associated genes that are induced by TSA/AzaC in neurosphere cells, including Cd34, Cd133, Oct4, Nanog, Klf4, Bex1, and the Dppa family members Dppa2, 3, 4, and 5. Sox2 and c-Myc are constitutively expressed in neurosphere cells. We propose a model in which TSA/AzaC, by removal of epigenetic inhibition, induces the reactivation of several stem cell and pluripotency-associated genes, and their coordinate expression enlarges the differentiation potential of somatic precursor cells. Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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