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. 2021 Sep 29;13:738529. doi: 10.3389/fnagi.2021.738529

TABLE 1.

The transdifferentiation of fibroblasts to neurons and dopamine neurons by direct reprogramming.

Source cells Induced cells Transcription factors/miRNA/chemicals Efficiency Transplantation Investigators PMID
Mouse embryonic and postnatal fibroblasts Functional neurons Ascl1, Brn2, and Myt1l 19.55% neurons No Vierbuchen et al., 2010 20107439
Human fibroblasts Dopaminergic neurons Ascl1, Brn2, Myt11, Lmx1a, FoxA2 16% neurons; 4.3% DA neurons No Pfisterer et al., 2011 21646515
Mouse and human fibroblasts Functional dopaminergic neurons Mash1 (Ascl1), Nurr1 (Nr4a2), and Lmx1a 10% neurons; 5% DA neurons No Caiazzo et al., 2011 21725324
Human fetal lung fibroblasts DA neurons Mash1, Ngn2, Sox2, Nurr1, and Pitx3 Less than 4% DA neurons Yes Liu et al., 2012 22105488
Mouse fibroblasts Induced neurons and DA neurons Ascl1 and Nurr1 and neurotrophic factors including SHH and FGF8b 51% Tuj1+ neurons, 33% DA neurons No Oh et al., 2014 24991651
Human embryonic fibroblasts Induced neurons Ascl1,Brn2,Myt1l, small molecules MAp2 + neurons 46% Yes Pereira et al., 2014 25208484
Mouse fibroblasts Dopaminergic precursors Brn2, Sox2 and Foxa2, SHH, and FGF8 TH+ 90% of the Tuj1+ neurons Yes Tian et al., 2015 26224135
Human fetal lung fibroblast Dopaminergic neurons Ascl1, Nurr1, Lmx1a and miR124, p53 shRNA Tuj1+ cells 31.1 ± 1.9%; TH+ cells (15.4 ± 1.1%) No Jiang et al., 2015 26639555
Human fibroblasts Neurons/dopaminergic neurons Brn2, Sox2, and Foxa2 96.67 and 86.75% expressing TH+/NeuN+ and TH+/MAP2+ No He et al., 2019 30664902
Mouse and human Astrocytes and Foreskin fibroblasts Functional noradrenergic neurons Ascl1, Phox2b, Ap-2a, Gata3, Hand2, Nurr1, andPhox2a 6.6 ± 1.0%TH+ neuron Yes Li et al., 2019 31315047
Human postnatal and adult fibroblasts Striatal neurons, GABAergic neurons miR-9/9*-124 with CTIP2 (BCL11B) DLX1, DLX2, MYT1L 90% MAP2+, and 84% NeuN+; 72.3% GABAergic neurons of MAP2+ cells Yes Victor et al., 2014 25374357
Human fetal lung fibroblast Neurons/iDA neurons miR124, p53 shRNA, Ascl1, Nurr1, and Lmx1a 31.1% Tuj1+ cells, 15.4% TH+ cells No Jiang et al., 2015 26639555
Human dermal fibroblasts Neural precursor cells, GABAergic or glutamatergic neurons cmRNA SOX2 and cmRNA PAX6 38% TUJ1+ neurons No Connor et al., 2018 30450440
Mouse embryonic fibroblasts and adult tail-tip fibroblasts Neural stem cells, neurons Valproic acid, Bix01294, RG108, PD0325901, CHIR99021, Vitamin C, and A83-01 treatment 31% neurons expressing MAP2+ Yes Han et al., 2016 26788068
Mouse fibroblasts Neuron-like cells VPA, TD114-2 (CHIR99021), 616452, Tranylcypromine, Forskolin, AM580, EPZ004777 50% of cells expressing tau, Tuj1 and MAP2 Yes Li et al., 2017 28648365
Human dermal fibroblasts Neuron-like cells Ngn2 and Ascl1; LDN-193189, A83-1, CHIR99021, Forskolin, SB-431542, Pyrintegrin, ZM336372, AZ960, and KC7F2 80% of cells expressing Tuj1 and NeuN No Herdy et al., 2019 31099332
Fibroblasts Induced neuronal cells Fusion protein of 30Kc19 and Ascl1 Not indicated No Ryu et al., 2020 32058047
Mouse embryo fibroblasts Induced neuronal cells PTB-shRNA Not indicated No 23313552
Mouse astrocytes in vivo Induced dopamine neuron NEUROD1, ASCL1 and LMX1A, and miR218 30.97% neurons and 16% induced dopamine neuron Yes Rivetti Di Val Cervo et al., 2017 28398344
Mouse muller glia and astrocytes in striatum mouse Induced neuron conversion CasRx gene with two gRNAs 5 and 6 to knockdown Ptbp1 32% TH+ cells Yes Zhou et al., 2020 32272060
Astrocytes in the middle brain Neurons, DA neurons PTB-shRNA 80% of cells expressing NeuN; 22% of cell expressed TH and GIRK2 (A9 DA neurons) No Qian H. et al., 2020 32581380