| First Author | Raciti M | Year | 2013 |
| Journal | Mol Cell Neurosci | Volume | 57 |
| Pages | 42-53 | PubMed ID | 24128663 |
| Mgi Jnum | J:215737 | Mgi Id | MGI:5606155 |
| Doi | 10.1016/j.mcn.2013.10.004 | Citation | Raciti M, et al. (2013) Reprogramming fibroblasts to neural-precursor-like cells by structured overexpression of pallial patterning genes. Mol Cell Neurosci 57:42-53 |
| abstractText | In this study, we assayed the capability of four genes implicated in embryonic specification of the cortico-cerebral field, Foxg1, Pax6, Emx2 and Lhx2, to reprogramme mouse embryonic fibroblasts towards neural identities. Lentivirus-mediated, TetON-dependent overexpression of Pax6 and Foxg1 transgenes specifically activated the neural stem cell (NSC) reporter Sox1-EGFP in a substantial fraction of engineered cells. The efficiency of this process was enhanced up to ten times by simultaneous inactivation of Trp53 and co-administration of a specific drug mix inhibiting HDACs, H3K27-HMTase and H3K4m2-demethylase. Remarkably, a fraction of the reprogrammed population expressed other NSC markers and retained its new identity, even after switching off the reprogramming transgenes. When transferred into a pro-differentiative environment, Pax6/Foxg1-overexpressing cells activated the neuronal marker Tau-EGFP. Frequency of Tau-EGFP positive cells was almost doubled upon delayed delivery of Emx2 and Lhx2 transgenes. A further improvement of the neuron-like cell output was achieved by inhibition of the BMP and TGFbeta pathways. Tau-EGFP positive cells were able to generate action potentials upon injection of depolarizing current pulses, further indicating their neuron-like phenotype. |
