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.
Original language | English (US) |
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Article number | 110849 |
Journal | Cell Reports |
Volume | 39 |
Issue number | 11 |
DOIs | |
State | Published - Jun 14 2022 |
Keywords
- CP: Cell biology
- Mϋller glia
- PTBP1
- Ptbp1
- RNA splicing
- cell reprogramming
- glia-to-neuron conversion
- regeneration
- retina
- retinal ganglion cell
- transdifferentiation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology