Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression

Expression of the transcription factors Oct4, Sox2, Klf4, and c‐Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and β cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2008-10, Vol.26 (10), p.2467-2474
Main Authors: Eminli, Sarah, Utikal, Jochen, Arnold, Katrin, Jaenisch, Rudolf, Hochedlinger, Konrad
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Cell Differentiation
Cell Line
Cellular Reprogramming
Green Fluorescent Proteins - metabolism
Humans
Induced pluripotent stem cells
Mice
Mice, Inbred C57BL
Neural progenitor cells
Neurons - cytology
Neurons - metabolism
Oct4
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Recombinant Fusion Proteins - metabolism
Reprogramming
Sox2
SOXB1 Transcription Factors - metabolism
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Summary:Expression of the transcription factors Oct4, Sox2, Klf4, and c‐Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and β cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are equally amenable to reprogramming into iPS cells by the same combination of factors. To test this, we have isolated genetically marked neural progenitor cells (NPCs) from neonatal mouse brains and infected them with viral vectors expressing Oct4, Sox2, Klf4, and c‐Myc. Infected NPCs gave rise to iPS cells that expressed markers of embryonic stem cells, showed demethylation of pluripotency genes, formed teratomas, and contributed to viable chimeras. In contrast to other somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did not require viral Sox2 expression for reprogramming into iPS cells. Our data show that in addition to mesoderm‐ and endoderm‐derived cell types, neural progenitor cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting that in vitro reprogramming is a universal process. These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context. Disclosure of potential conflicts of interest is found at the end of this article.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2008-0317