Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina

Ye Xie, Jing Zhou, Bo Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Reprogramming glial cells to convert them into neurons represents a potential therapeutic strategy that could repair damaged neural circuits and restore function. Recent studies show that downregulation of the RNA-binding protein PTBP1 leads to one-step conversion of Müller glia (MG) into retinal ganglion cells (RGCs) with a high efficiency. However, the original study did not perform fate-mapping experiments to confirm MG-to-RGC conversion after Ptbp1 downregulation. To address the fundamental question of whether Ptbp1 downregulation can convert MG into RGCs in the mouse retina, we perform fate-mapping experiments to lineage trace MG independent of the adeno-associated virus (AAV)-mediated labeling system. Here, we report that Ptbp1 downregulation by CRISPR-CasRx or small hairpin RNA is insufficient to convert MG to RGCs. The original conclusion of MG-to-RGC conversion is due to leaky labeling of endogenous RGCs. Our results emphasize the importance of using stringent fate mapping to determine glia-to-neuron conversion in cell reprogramming research.

Original languageEnglish
Article number110960
JournalCell Reports
Volume39
Issue number11
DOIs
StatePublished - 14 Jun 2022

Keywords

  • CP: Neuroscience
  • CP: Stem cell research
  • Müller glia
  • fate mapping
  • glia-to-neuron conversion
  • lineage tracing
  • reprogramming
  • retinal ganglion cells

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