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