Hypoxia supports reprogramming of mesenchymal stromal cells via induction of embryonic stem cell-specific microRNA-302 cluster and pluripotency-associated genes
| Autor: | Insa S. Schroeder, Bernadette Harwardt, Matthias Jung, Sabine Foja, Dagmar Riemann, Oliver Pelz-Ackermann |
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| Rok vydání: | 2012 |
| Předmět: |
Homeobox protein NANOG
Pluripotent Stem Cells Rex1 Biology SOX2 Humans Induced pluripotent stem cell Embryonic Stem Cells Cell Line Transformed Homeodomain Proteins Mesenchymal stem cell Nanog Homeobox Protein Mesenchymal Stem Cells Cell Biology Cell Dedifferentiation Molecular biology Cell Hypoxia Cell biology MicroRNAs Multigene Family embryonic structures Fibroblast Growth Factor 2 biological phenomena cell phenomena and immunity Stem cell Reprogramming Octamer Transcription Factor-3 Developmental Biology Biotechnology |
| Zdroj: | Cellular reprogramming. 15(1) |
| ISSN: | 2152-4998 |
| Popis: | Pluripotency is characterized by specific transcription factors such as OCT4, NANOG, and SOX2, but also by pluripotency-associated microRNAs (miRs). Somatic cells can be reprogrammed by forced expression of these factors leading to induced pluripotent stem cells (iPSCs) with characteristics similar to embryonic stem cells (ESCs). However, current reprogramming strategies are commonly based on viral delivery of the pluripotency-associated factors, which affects the integrity of the genome and impedes the use of such cells in any clinical application. In an effort to establish nonviral, nonintegrating reprogramming strategies, we examined the influence of hypoxia on the expression of pluripotency-associated factors and the ESC-specific miR-302 cluster in primary and immortalized mesenchymal stromal cells (MSCs). The combination of hypoxia and fibroblast growth factor 2 (FGF2) treatments led to the induction of OCT4 and NANOG in an immortalized cell line L87 and primary MSCs, accompanied with increased doubling rates and decreased senescence. Most importantly, the endogenous ECS-specific cluster miR-302 was induced upon hypoxic culture and FGF2 supplementation. Hypoxia also improved reprogramming of MSCs via episomal expression of pluripotency factors. Thus, our data illustrate that hypoxia in combination with FGF2 supplementation efficiently facilitates reprogramming of MSCs. |
| Databáze: | OpenAIRE |
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