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- Title
Transcription factor-based modulation of neural stem cell differentiation using direct protein transduction.
- Authors
Stock, Kristin; Nolden, Lars; Edenhofer, Frank; Quandel, Tamara; Brüstle, Oliver
- Abstract
In contrast to conventional gene transfer strategies, the direct introduction of recombinant proteins into cells bypasses the risk of insertional mutagenesis and offers an alternative to genetic intervention. Here, we explore whether protein transduction of the gliogenic transcription factor Nkx2.2 can be used to promote oligodendroglial differentiation of mouse embryonic stem cell (ESC)-derived neural stem cells (NSC). To that end, a recombinant cell-permeant form of Nkx2.2 protein was generated. Exposure of ESC-derived NSC to the recombinant protein and initiation of differentiation resulted in a two-fold increase in the number of oligodendrocytes. Furthermore, Nkx2.2-transduced cells exhibited a more mature oligodendroglial phenotype. Comparative viral gene transfer studies showed that the biological effect of Nkx2.2 protein transduction is comparable to that obtained by lentiviral transduction. The results of this proof-of-concept study depict direct intracellular delivery of transcription factors as alternative modality to control lineage differentiation in NSC cultures without genetic modification.
- Subjects
GENETIC transduction; TRANSCRIPTION factors; NEURAL stem cells; CELL differentiation; OLIGODENDROGLIA
- Publication
Cellular & Molecular Life Sciences, 2010, Vol 67, Issue 14, p2439
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-010-0347-1