Generation of diverse neural cell types through direct conversion

Table 1 Summary of studies demonstrating generation of functional induced neuronal cells by direct conversion

Species	Original cell	Transgenes	Method	End cell	Ref.
Mouse	Fibroblast	BAM	iLV	iN	[16]
Human	Fibroblast	BAM, NeuroD1	iLV	iN	[71]
Human	Fibroblast	miR-9/9*-124, Ascl1, Myt1l, NeuroD2	LV	iN	[83]
Human	Fibroblast	BAM	iLV	iN	[153]
Human	Fibroblast	miR-124, Brn2, Myt1l	iLV	iN	[84]
Mouse	Hepatocyte	BAM	iLV	iN	[73]
Human	Fibroblast	Ascl1, Ngn2	iLV	iN	[74]
Human	Pericyte	Ascl1, Sox2	RV	iN	[76]
Mouse	Fibroblast	Brn2, Ascl1, Ngn2	AV	iN	[144]
Human	Cord blood cell	Sox2	RV	iN	[75]
Human	Cord blood cell	Sox2, c-Myc	RV	iN	[75]
Human	Glioma cell	Brn2, Ascl1, Ngn2	LV	iN	[77]
Mouse	Fibroblast	BAM	NV	iN	[147]
Mouse	Adipocyte progenitor cell	BAM	iLV	iN	[78]
Mouse	Fibroblast	shR-PTB	LV	iN	[85]
Human	Fibroblast	Ascl1, Myt1l, Sox2	LV	iN	[154]
Common marmoset	Fibroblast	BAM, NeuroD1	iLV	iN	[72]
Human	Fibroblast	BAM	iLV	iN	[81]
Mouse	Fibroblast	Ascl1	iLV	iN	[155]
Human	Fibroblast	Ascl1	iLV	iN	[155]
Mouse	Astroglia	Ink4a/Arf-/-, Dlx2	iLV	iN	[79]
Mouse	Fibroblast	Ink4a/Arf-/-, BAM	iLV	iN	[79]
Mouse	Fibroblast	Brn2, Ascl1, Ngn2, Rarg, Nr5a2	AV	iN	[80]
Human	Fibroblast	Brn2, Ascl1, Ngn2, Rarg, Nr5a2	AV	iN	[80]
Human	Fibroblast	shR-p16-19	LV	iN	[82]
Human	Fibroblast	hTERT	LV	iN	[82]

BAM: Brn2, Ascl1, and Myt1l; miR: MicroRNA; shR: Small hairpin RNA; PTB: Polypyrimidine-tract-binding protein; iLV: Inducible lentiviral vector; LV: Lentiviral vector; RV: Retroviral vector; AV: Adenoviral vector; NV: Non-viral; iN: Induced neuron.

Table 2 Summary of studies demonstrating generation of functional induced neuronal subtypes by direct conversion

Species	Original cell	Transgenes	Method	End cell	Ref.
Human	Fibroblast	BAM, Lmx1a, FoxA2	iLV	iDN	[87]
Mouse	Fibroblast	Ascl1, Nurr1, Lmx1a	iLV	iDN	[88]
Human	Fibroblast	Ascl1, Nurr1, Lmx1a	iLV	iDN	[88]
Mouse	Fibroblast	BAM, Lhx3, Hb9, Isl1, Ngn2	RV	iMN	[93]
Human	Fibroblast	BAM, Lhx3, Hb9, Isl1, Ngn2, NeuroD1	RV	iMN	[93]
Mouse	Fibroblast	Ascl1, Pitx3, Lmx1a, Nurr1, FoxA2, EN1	iLV	iDN	[89]
Mouse	Astrocyte	Ascl1, Lmx1b, Nurr1	iLV	iDN	[92]
Mouse	Fibroblast	Ascl1, Lmx1b, Nurr1	iLV	iDN	[92]
Mouse	Cord blood-derived stem cell	Ascl1, Lmx1b, Nurr1	iLV	iDN	[92]
Human	Fibroblast	Ascl1, Ngn2, Sox2, Nurr1, Pitx3	LV	iDN	[90]
Mouse	Fibroblast	Brn2, Ascl1, Lmx1b, Nurr1, Otx2	RV	iDN	[91]
Mouse	Fibroblast	Brn2, Ascl1, Ngn2, Pax6, Hes1, Id1, c-Myc, Klf4	RV	iNPC → iDN	[91]
Human	Fibroblast	Ngn2	RV	iMN	[94]
Human	Fibroblast	BAM, Lmx1a, Lmx1b, FoxA2, Otx2	iLV	iDN	[81]
Human	Fibroblast	Ascl1, Ngn2, Sox2, Nurr1, Pitx3, p53-DN	LV	iDN	[156]
Human	Fibroblast	miR-9/9*-124, Myt1l, Bcl11b, Dlx1, Dlx2	iLV	iMSN	[95]
Mouse	Fibroblast	Brn3a, Ngn1/2	iLV	iSN	[96]
Human	Fibroblast	Brn3a, Ngn1/2	iLV	iSN	[96]
Mouse	Fibroblast	Nfia, Nfib, Sox9	iLV	iA	[97]
Human	Fibroblast	Nfia, Nfib, Sox9	iLV	iA	[97]

BAM: Brn2, Ascl1, and Myt1l; miR: MicroRNA; shR: Small hairpin RNA; iLV: Inducible lentiviral vector; LV: Lentiviral vector; iN: Induced neuron; iNPC: Induced neural progenitor cell; iDN: Induced dopaminergic neuron; iMN: Induced motor neuron; iMSN: Induced medium spiny neuron; iSN: Induced sensory neuron; iA: Induced astrocyte.

Table 3 Summary of studies demonstrating generation of functional induced neural stem and progenitor cells by direct conversion

Species	Original cell	Transgenes	Method	End cell	Ref.
Mouse	Fibroblast	OSKM	iLV	iNPC	[101]
Human	Melanocyte	Notch1	LV	iNCC	[102]
Human	Astrocyte	4-Oct	LV	iNSC	[110]
Human	Astrocyte	Sox2	LV	iNSC	[110]
Human	Astrocyte	Nanog	LV	iNSC	[110]
Mouse	Fibroblast	Brn4, Sox2, Klf4, c-Myc, E47	RV	iNSC	[105]
Human	Fibroblast	Oct4, Sox2, Klf4, Zic3	RV	iNPC	[104]
Mouse	Fibroblast	Brn2, Sox2, FoxG1	iLV	iNPC	[123]
Mouse	Fibroblast	OSKM	RV	iNSC	[116]
Human	Fibroblast	OSKM	RV	iNSC	[116]
Human	Fibroblast	Sox2, Pax6	NV	iNPC	[98]
Mouse	Fibroblast	Sox2	RV	iNSC	[122]
Human	Fibroblast	Sox2	RV	iNSC	[122]
Mouse	Sertoli cell	Ascl1, Ngn2, Hes1, Id1, Pax6, Brn2, Sox2, c-Myc, Klf4	RV	iNSC	[111]
Mouse	Fibroblast	OSKM	RV/iLV	iNSC	[117]
Mouse	Fibroblast	Brn2, Nr2e1, Sox2, c-Myc, Bmi1	RV	iNPC	[157]
Human	Fibroblast	OSKM	SV	iNPC	[118]
Monkey	Fibroblast	OSKM	SV	iNPC	[118]
Mouse	Fibroblast	Sox10, Olig2, Nkx6.2	LV	iOPC	[107]
Human	Urine cells	Oct4, Sox2, Klf4, SV40LT, miR-302-367	NV	iNPC	[112]
Mouse	Fibroblast	Sox10, Olig2, Zfp536	iLV	iOPC	[108]
Rat	Fibroblast	Sox10, Olig2, Zfp536	iLV	iOPC	[108]
Human	Fibroblast	Oct3, Sox2, Klf4, c-Myc	RV	iNPC	[125]
Mouse	Fibroblasts	Brn2, Hes1, Hes3, Klf4, c-Myc, Plagl1, Notch1 (NICD), Rfx4	NV	iNSC	[99]
Mouse	Liver cells	Brn2, Hes1, Hes3, Klf4, c-Myc, Plagl1, Notch1 (NICD), Rfx4	NV	iNSC	[99]
Mouse	Blymphocytes	Brn2, Hes1, Hes3, Klf4, c-Myc, Plagl1, Notch1 (NICD), Rfx4	NV	iNSC	[99]
Mouse	Fibroblast	OSKM	iLV	iDNPC	[109]
Rat	Bone marrow-derived stem cell	Ngn2	LV	iNPC	[114]
Mouse	Fibroblast	Sox2, Klf4, c-Myc, Brn4	RV	iNSC	[158]
Human	Fibroblast	Sox10	iLV	iNCC	[103]
Human	Fibroblast	4-Oct	LV	iNPC	[121]
Pig	Fibroblast	Oct4, Sox2, Klf4, Lin28, L-Myc	NV	iNPC	[120]
Human	Fibroblast	4-Oct	LV	iNSC	[119]
Human	Fibroblast	Oct4, Sox2, Klf4, shR-p53	NV	iNSC	[119]
Human	Fibroblast	Sox2, c-Myc, Brn2	LV	iNPC	[159]
Human	Fibroblast	Sox2, c-Myc, Brn4	LV	iNPC	[159]
Human	Astrocyte	miR-302/367	LV	iNB	[106]
Human	Fibroblast	Sox2, HMGA2	RV	iNSC	[113]
Human	Cord blood-derived stem cell	Sox2, HMGA2	RV	iNSC	[113]

OSKM: Oct4, Sox2, Klf4, c-Myc; miR: MicroRNA; shR: Small hairpin RNA; NICD: Notch intracellular domain; HMGA2: High-mobility group A2; iLV: Inducible lentiviral vector; LV: Lentiviral vector; RV: Retroviral vector; SV: Sendai virus vector; NV: Non-viral; iNCC: Induced neural crest cell; iNSC: Induced neural stem cell; iNPC: Induced neural progenitor cell; iOPC: Induced oligodendrocyte progenitor cell; iDNPC: Induced dopaminergic neuronal progenitor cell; iNB: Induced neuroblast.