Generation of XXXX Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage.

@entity35 @entity19 @entity935 @entity191 @entity11408 @entity51783 @entity5613 @entity54223 @entity72969 @entity55236 @entity7004
Recent groundbreaking work has demonstrated that combined expression of the transcription factors @entity51783 , @entity7004 , and @entity72969 (BAM; also known as Wernig factors) convert @entity19 fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating @entity11408 differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and @entity5613 induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common @entity11408 genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of @entity55236 and @entity54223 , transcription factors specific for midbrain @entity935 neuron development, drove iNPCs to yield mature midbrain @entity935 neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in @entity191 model @entity35 .
