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Table 3 Studies reporting lack of glia-to-neuron conversion following PTBP1 knockdown

From: Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson’s and Alzheimer’s disease

Research group & reference

Intended target cell population

Intended CNS region

Animal model(s)

Targeting vector(s)

Lineage tracing

Detection method

Target sequence(s)

Improvements in animal model?

C.L. Zhang (Wang et al. (2021))

[30]

Astrocytes

Striatum

Young WT mice

AAV2/5-shPtbp1 (same sequence as Qian et al. (2020))

Aldh1l1-CreERT2;R26R-YFP and mGfap-Cre;R26R-YFP

Lineage reporter and viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ

(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

AAV2/5-LSL-shPtbp1 (same sequence as Qian et al. 2020))

Aldh1l1-CreERT2;R26R-YFP and mGfap-Cre;R26R-YFP

Lineage reporter and Cre-dependent viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ

(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

AAV2/2-LSL-shPtbp1 (vector from Qian et al. 2020))

mGfap-Cre;R26R-YFP

Lineage reporter and Cre-dependent viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

AAV2/5-LSL-shPtbp1 (vector from Qian et al. 2020))

mGfap-Cre;R26R-YFP

Lineage reporter and Cre-dependent viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

AAV2/2-LSL-shPtbp1 (virus from Qian et al. (2020))

mGfap-Cre;R26R-YFP

Lineage reporter and Cre-dependent viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

AAV2/PHP.eB-CRISPR-CasRX (vector from Zhou et al. (2020))

mGfap-Cre;R26R-YFP

Lineage reporter and viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ(exon 10 of mouse Ptbp1)

Not done – no generation of new neurons in vivo

S. Blackshaw (Hoang et al. (2023))

[63]

Astrocytes

Striatum

PD (6-OHDA)

Astrocyte-specific gene deletion

Aldh1l1-CreERT2;Sun1- GFPlox/lox; Ptbp1lox/lox

Viral reporter

N/A

No generation of new neurons in vivo

Cortex

PD (6-OHDA)

Astrocyte-specific gene deletion

Aldh1l1-CreERT2;Sun1- GFPlox/lox; Ptbp1lox/lox

Viral reporter

N/A

No generation of new neurons in vivo

SNpc

PD (6-OHDA)

Astrocyte-specific gene deletion

Aldh1l1-CreERT2;Sun1- GFPlox/lox; Ptbp1lox/lox

Viral Cre-induced reporter

N/A

No generation of new neurons in vivo

S. Blackshaw (Hoang et al. (2022))

[28]

Müller glia

Retina

NMDA injured mice

Müller glia-specific gene deletion

Glast-CreERT2;Sun1-

GFPlox/lox;Ptbp1lox/lox

Viral Cre-induced reporter

N/A

Yes but unlikely to have resulted from Ptbp1 loss of function

B.L. Davidson (Leib et al. (2022))

[64]

Astrocytes

Striatum, cortex and hippocampus

Not done

AAV2/1-miPtbp1

Aldh1l1-CreERT2;R26R-tdTomato

Lineage reporter

5ʹ -CTCAATGTCAAGTACAACAAT-3’

(exon 7 of mouse Ptbp1)

No generation of new neurons in vivo

M. Li (Chen et al. (2022))

[29]

Astrocytes

Striatum

PD (6-OHDA)

AAV2/5-shPtbp1

Aldh1l1-CreERT2;rpl22lsl-HA

Lineage reporter and viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ

(exon 10 of mouse Ptbp1)

No generation of new neurons in vivo

SNpc

PD (6-OHDA)

Anti-Ptbp1 ASO

Aldh1l1-CreERT2;rpl22lsl-HA

Lineage reporter and viral reporter

5ʹ-GTGGAAATATTGCTAGGCAC-3ʹ(same sequence as ASO2 in Maimon et al. (2021) targeting 5ʹ UTR of mouse Ptbp1)

No generation of new neurons in vivo

B. Chen (Xie et al. (2022))

[65]

Müller glia

Retina

NMDA-injured mice

AAV-CMV-LSL-RFP-shPtbp1 (same vector as Qian et al. (2020))

Glast-CreERT2;Sun1-

GFPlox/lox

Lineage reporter and Cre-dependent viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3ʹ

(exon 10 of mouse Ptbp1)

No

AAV-GFAP-CasRx-Ptbp1 (same vector as Zhou et al. (2020))

Glast-CreERT2;Sun1-

GFPlox/lox

Lineage reporter and viral reporter

Same guide RNA sequences as Zhou et al. (2020).

No

Y. Zhao (Guo et al. 2022)

[76]

Astrocytes

Hippocampus

AD (5xFAD and PS19 mice), WT mice

AAV2/9-shPtbp1

Not done

Viral reporter

5ʹ-GGGTGAAGATCCTGTTCAATA-3

(Same sequence as Qian et al. (2020) targeting exon 10 of mouse Ptbp1)

No

K. Fang (Yang et al. 2023)

[66]

Astrocytes

Striatum

Mouse WT

AAV-PHP.eB-Cas13X-NLS-HA-sgPtbp1

AAV-GFAP::tdTomato-WPRE

Lineage reporter

Vector sequnces provided in methods and supplemntary information

No

  1. Table adapted from Wang & Zhang (2024) [62]. 6-OHDA, 6-hydroxydopamine; AAV, adeno-associated virus; ASO, antisense oligonucleotide; NMDA, N-methyl-d-aspartate; miRNA, micro-RNA; SNpc, substantia nigra pars compacta; WT, wild type