Induced Pluripotency and Oncogenic Transformation Are Related Processes
| Autor: | Kelly M. Bush, John W. Riggs, Vanessa Chan, Bonnie L. Barrilleaux, Natasha Varlakhanova, Paul S. Knoepfler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cell type
Induced Pluripotent Stem Cells Gene Expression Mice SCID Biology Regenerative medicine Transcriptome Proto-Oncogene Proteins c-myc Mice Downregulation and upregulation Mice Inbred NOD Gene expression Animals Induced pluripotent stem cell Gene Cells Cultured Embryonic Stem Cells Issues in Development Oligonucleotide Array Sequence Analysis Genetics Regulation of gene expression Cell Differentiation Cell Biology Hematology Neoplasms Experimental Fibroblasts Antigens Differentiation Coculture Techniques Cell biology Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Developmental Biology |
| Popis: | Induced pluripotent stem cells (iPSCs) have the potential for creating patient-specific regenerative medicine therapies, but the links between pluripotency and tumorigenicity raise important safety concerns. More specifically, the methods employed for the production of iPSCs and oncogenic foci (OF), a form of in vitro produced tumor cells, are surprisingly similar, raising potential concerns about iPSCs. To test the hypotheses that iPSCs and OF are related cell types and, more broadly, that the induction of pluripotency and tumorigenicity are related processes, we produced iPSCs and OF in parallel from common parental fibroblasts. When we compared the transcriptomes of these iPSCs and OF to their parental fibroblasts, similar transcriptional changes were observed in both iPSCs and OF. A significant number of genes repressed during the iPSC formation were also repressed in OF, including a large cohort of differentiation-associated genes. iPSCs and OF shared a limited number of genes that were upregulated relative to parental fibroblasts, but gene ontology analysis pointed toward monosaccharide metabolism as upregulated in both iPSCs and OF. iPSCs and OF were distinct in that only iPSCs activated a host of pluripotency-related genes, while OF activated cellular damage and specific metabolic pathways. We reprogrammed oncogenic foci (ROF) to produce iPSC-like cells, a process dependent on Nanog. However, the ROF had reduced differentiation potential compared to iPSC, suggesting that oncogenic transformation leads to cellular changes that impair complete reprogramming. Taken together, these findings support a model in which OF and iPSCs are related, yet distinct cell types, and in which induced pluripotency and induced tumorigenesis are similar processes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|