Direct Conversion of Fibroblasts into Stably Expandable Neural Stem Cells
| Autor: | Frank Edenhofer, Dominic Seiferling, Marc Thier, Tamara Quandel, Per Hoffmann, Oliver Brüstle, Raphaela Gorris, Markus M. Nöthen, Thoralf Opitz, Yenal Bernard Lakes, Stefan Herms, Philipp Wörsdörfer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Somatic cell
metabolism [Neural Stem Cells] Mice 0302 clinical medicine Neural Stem Cells cytology [Fibroblasts] cytology [Neural Stem Cells] reproductive and urinary physiology cytology [Astrocytes] Neurons 0303 health sciences metabolism [Astrocytes] Brain Cell Differentiation cytology [Induced Pluripotent Stem Cells] Neural stem cell Cell biology metabolism [Induced Pluripotent Stem Cells] Oligodendroglia metabolism [Neurons] KLF4 Molecular Medicine biological phenomena cell phenomena and immunity Reprogramming metabolism [Fibroblasts] transplantation [Neural Stem Cells] Induced Pluripotent Stem Cells Transplantation Heterologous Biology biosynthesis [Transcription Factors] metabolism [Oligodendroglia] OLIG2 03 medical and health sciences Kruppel-Like Factor 4 SOX2 ddc:570 Genetics Animals cytology [Oligodendroglia] 030304 developmental biology transplantation [Induced Pluripotent Stem Cells] cytology [Brain] Cell Biology Nestin Cell Dedifferentiation Fibroblasts Molecular biology Rats nervous system metabolism [Brain] Astrocytes cytology [Neurons] PAX6 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Cell Stem Cell Cell Stem Cell; Vol 10 Cell stem cell 10(4), 473-479 (2012). doi:10.1016/j.stem.2012.03.003 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2012.03.003 |
| Popis: | SummaryRecent advances have suggested that direct induction of neural stem cells (NSCs) could provide an alternative to derivation from somatic tissues or pluripotent cells. Here we show direct derivation of stably expandable NSCs from mouse fibroblasts through a curtailed version of reprogramming to pluripotency. By constitutively inducing Sox2, Klf4, and c-Myc while strictly limiting Oct4 activity to the initial phase of reprogramming, we generated neurosphere-like colonies that could be expanded for more than 50 passages and do not depend on sustained expression of the reprogramming factors. These induced neural stem cells (iNSCs) uniformly display morphological and molecular features of NSCs, such as the expression of Nestin, Pax6, and Olig2, and have a genome-wide transcriptional profile similar to that of brain-derived NSCs. Moreover, iNSCs can differentiate into neurons, astrocytes, and oligodendrocytes. Our results demonstrate that functional NSCs can be generated from somatic cells by factor-driven induction. |
| Databáze: | OpenAIRE |
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