How to reprogram human fibroblasts to neurons

Xu, Ziran; Su, Shengnan; Zhou, Siyan; Yang, Wentao; Deng, Xin; Sun, Yingying; Li, Lisha; Li, Yulin

doi:10.1186/s13578-020-00476-2

Cell & Bioscience

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]
Excitatory neurons	NEUROD1	Improve the efficiency of reprogramming human fibroblasts into TUJ1 positive neurons	Pang et al. 2011 [19]
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]
Motor neurons	HB9, LSL1, NGN2	Improve the efficiency of reprogramming human fibroblasts into induced motor neurons (iMN)	Son et al. 2011 [41]
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]
Neurons	miR-124	Turn off the reprogramming gene expression of stable neurons by regulating the reprogramming gene; promote neurogenesis and regulate the activity of neurons	Lau et al. 2014 [48]
Nociceptor, mechanoreceptor, proprioceptor neurons	BRN3A	A necessary factor for the differentiation of sensory neurons	Blanchard et al. 2015 [99]
Nociceptor, mechanoreceptor, proprioceptor neurons	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	Blanchard et al. 2015 [99]
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]
Neurons (GABAergic and glutamate-energy neurons)	NGN2	Guide progenitor cells differentiating to neurons during development; improve the reprogramming efficiency of human fibroblasts into neurons	Zhao et al. 2015 [100]
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]
Motor neurons	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	Abernathy et al. 2017 [91]
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

Back to article page

ISSN: 2045-3701

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com

You are viewing the site in preview mode

Cell & Bioscience

Contact us