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Chunk #7 — 3. Induced neuronal cells — 3.2. Crossing major lineage boundaries: mesodermal to ectodermal conversion

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Induced neuronal reprogramming.
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together with two other transcription factors, Brn2 and Myt1l, in defined conditions are enough to convert human postnatal and adult fibroblasts into mostly excitatory neuronal cells [22]. Remarkably, in their transcription factor combination, the authors did not use any of the neurogenic basic-helix-loop-helix transcription factors reported by our group and others [21, 23] although this family of transcription factors has the most pervasive role in neuronal development and are therefore considered the strongest drivers of reprogramming [24]. Indeed, our recent molecular insights into the reprogramming process revealed the critical contributions of Ascl1 and we could demonstrate that this bHLH factor alone is sufficient to induce fully functional iN cells from fibroblasts [25, 26]. Future studies will show whether the Brn2, Myt1l, miR-124 factor combination induces endogenous expression of bHLH transcription factors in fibroblasts and whether this induction is essential for reprogramming. Transfection of miR-124 in P19 cells led to markedly increased expression of the two bHLH transcription factors Ngn2 and NeuroD1 [27]. More recently another study claimed the generation of iN cells from embryonic fibroblasts without use of bHLH factors by simple knock-down of the splicing factor PTB [28]. Those mouse iN cells surprisingly exhibited both spontaneous glutamatergic and GABAergic