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Table 1 Reprogram human fibroblasts into neurons using transcription factors since 2011

From: How to reprogram human fibroblasts to neurons

Target cell type Reprogramming factors Effects on neural cells induction References
Excitatory neurons BRN, ASCL1, MYT1L Convert human fibroblasts into functional neurons Pang et al. 2011 [19]
NEUROD1 Improve the efficiency of reprogramming human fibroblasts into TUJ1 positive neurons
Excitatory neurons ASCL1, MYT1L, NEUROD2 Improve the maturity of neurons which reprogram from human fibroblasts Yoo et.al. 2011 [42]
Improve the maturity of neurons which reprogram from human fibroblasts
Improve the maturity of neurons which reprogram from human fibroblasts
miR-9* Induce the transformation of human fibroblasts into neurons
miR-124 Induce the transformation of human fibroblasts into neurons
Excitatory neurons BRN2 Unknown Ambasudhan et al. 2011 [89]
MYTL1 Unknown
miR-124 Regulate the activity of major antineuronal differentiation factors in the central system;inhibit non-neuronal genes in post-transcriptional neurons
Dopaminergic neurons ASCL1 Convert human fibroblasts into neurons Pfisterer et al. 2011 [40]
LMX1A Promote conversion of neurons from human fibroblasts into dopaminergic neurons
BRN2 Convert human fibroblasts into neurons
MYT1L Convert human fibroblasts into neurons
FOXA2 Promote conversion of neurons from human fibroblasts into dopaminergic neurons
Dopaminergic neurons ASCL1 Reprogram fibroblasts into TH+ neurons by combining with Nurr1 Caiazzo et al. 2011 [43]
LMX1A Increase the efficiency of fibroblasts reprogramming into TH+ neurons by cooperating with Ascl1 and Nurr1
NURR1 The vital determinant of the specification and survival of dopaminergic neurons in development and adulthood
Motor neurons BRN2, ASCL1, MYT1L, NEUROD1, LHX3 Instruct the formation of motor neurons during development Son et al. 2011 [41]
HB9, LSL1, NGN2 Improve the efficiency of reprogramming human fibroblasts into induced motor neurons (iMN)
Dopaminergic neurons ASCL1 Neuronal determination function; promote the generation of mDA neurons by cooperating with Nurr1 and Ngn2 during midbrain development; promote the maturation of mDA neurons Liu et al. 2012 [21]
NGN2 Neuronal determination function; a necessary factor for mDA neuronal development
SOX2 A hallmark of nervous system, start with the development of the nervous system in selected brain regions and the maintenance of neurons
NURR1 Increase maturation of DA neurons reprogrammed by human fibroblasts
PITX3 Increase maturation of DA neurons reprogrammed by human fibroblasts
Neurons ASCL1 Reprogram human fibroblasts into neurons Chanda et al. 2014 [44]
Medium spiny neurons DLX1, DLX2 miR-9/9*-124 combining with DLX1 and DLX2 is vital important to MSN's terminal differentiation (Mutations of the homeobox genes DLX-1 and DLX-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons.) Victor et al. 2014 [98]
MYT1L Increase the number of MAP2 positive cells obtained by human fibroblasts reprogramming
CTIP2 Inhibit apoptosis of hematopoietic progenitor cells by overexpression
miR-9/9* Control the assembly of neuron-specific ATP-dependent chromatin remodeling complexes during neural development; regulate the expression of anti-nerve genes
miR-124 Control the assembly of neuron-specific ATP-dependent chromatin remodeling complexes during neural development; regulate the expression of anti-nerve genes
Neurons ASCL1, BRN2, MYT1L Unknown Lau et al. 2014 [48]
miR-124 Turn off the reprogramming gene expression of stable neurons by regulating the reprogramming gene; promote neurogenesis and regulate the activity of neurons
Nociceptor, mechanoreceptor, proprioceptor neurons BRN3A A necessary factor for the differentiation of sensory neurons Blanchard et al. 2015 [99]
NGN1 or NGN2 A necessary factor for the differentiation of sensory neurons; the precursors of sensory cells express NGN1 or NGN2; NGN1 and NGN2 may be transactivated or have overlapping/equivalent activities during the reprogramming of human fibroblasts into sensory neurons
Nociceptor neurons ASCL1, MYT1L Promote human fibroblasts reprogramming into different subtypes of neurons Wainger et al. 2015 [93]
ISL2 Effect is currently unclear, but the expression in situ shows more pain receptor specificity
KLF7 Maintain the expression of TRKA, promoting human fibroblasts reprogramming into nociceptors
NGN1 A necessary factor for the formation of nociceptor precursor expressing NTRK1 and postnatal nociceptors expressing TRPV1
Dopaminergic neurons ASCL1 Convert embryonic carcinoma cells into neurons, and lead to a rapid withdrawal of the cell cycle, possibly by inducing the cycle-dependent kinase inhibition P27KIP1 Jiang et al. 2015 [90]
NURR1 Unknown
LMX1A Unknown
miR-124 Significantly improve the efficiency of ANL (ASCL1, NURR1 and LMX1A) to generate TH+ cells; enhance the morphology of iDA neurons; increase the reprogramming efficiency of human fibroblasts into neurons
p53 shRNA Promote fibroblasts transformation into iDA neurons
Neurons (GABAergic and glutamate-energy neurons) ASCL1, SOX2 Reprogram human fibroblasts into neurons Zhao et al. 2015 [100]
NGN2 Guide progenitor cells differentiating to neurons during development; improve the reprogramming efficiency of human fibroblasts into neurons
Serotonergic neurons NKX2.2, FEV, GATA2, LMX1B Associated with serotonergic differentiation; be vital important for the specification and maturation of serotonergic neurons in the rodent midbrain dorsal raphe nuclei Vadodaria et al. 2016 [94]
ASCL1 Pro-neuronal transcription factors; be vital important for the specification and maturation of serotonergic neurons in the rodent midbrain dorsal raphe nuclei
NGN2 Pro-neuronal transcription factors
Motor neurons ISL1, LHX Reprogram human fibroblasts into MAP2, TUBB3 and NCAM positive cells with complex neuronal morphology by the co-expression of LHX3 and ISL1 with miR-9/9 *-124 Abernathy et al. 2017 [91]
miR-9/9* and miR-124 Trigger chromatin accessibility, DNA methylation, and reconfiguration of mRNA expression to induce the default neuronal state, but do not activate subtype-specific programs
Noradrenergic neurons ASCL1 Convert midbrain astrocytes into functional neurons Li et al. 2019 [95]
PHOX2B Induce noradrenergic neuronal phenotypes; key factor for noradrenergic neurons’ generation
AP-2Α Key factor for noradrenergic neurons’ generation
GATA3 GATA3 co-operating with Hand2
HAND2 Increases the level of noradrenaline released; key factors for noradrenergic neurons’ generation
NURR1 Promote the expression of mCherry and significantly increase the level of noradrenaline released; key factor for noradrenergic neurons’ generation
PHOX2A Key factor for noradrenergic neurons’ generation