Details

Autor(en) / Beteiligte

• Thier, Marc
• Wörsdörfer, Philipp
• Lakes, Yenal B.
• Gorris, Raphaela
• Herms, Stefan
• Opitz, Thoralf
• Seiferling, Dominic
• Quandel, Tamara
• Hoffmann, Per
• Nöthen, Markus M.
• Brüstle, Oliver
• Edenhofer, Frank

Titel

Direct Conversion of Fibroblasts into Stably Expandable Neural Stem Cells

Ist Teil von

• Cell stem cell, 2012-04, Vol.10 (4), p.473-479

Ort / Verlag

Cambridge, MA: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Recent 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. [Display omitted] ► Direct derivation of stably expandable neural stem cells (iNSCs) from mouse fibroblasts ► Restricted Oct4 activity during iPSC-type reprogramming promotes generation of iNSCs ► Maintenance of iNSCs does not depend on sustained expression of reprogramming factors ► iNSCs have a genome-wide transcriptional profile similar to that of brain-derived NSCs