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Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.

ABSTRACT: Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.

SUBMITTER: Hoang T

PROVIDER: S-EPMC9619396 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.

Hoang Thanh T Kim Dong Won DW Appel Haley H Pannullo Nicole A NA Leavey Patrick P Ozawa Manabu M Zheng Sika S Yu Minzhong M Peachey Neal S NS Blackshaw Seth S

Cell reports 20220601 11

Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozyg ...[more]

PMID: 35705053

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