| First Author | Xie Y | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 11 | Pages | 110960 |
| PubMed ID | 35705044 | Mgi Jnum | J:326052 |
| Mgi Id | MGI:7294008 | Doi | 10.1016/j.celrep.2022.110960 |
| Citation | Xie Y, et al. (2022) Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina. Cell Rep 39(11):110960 |
| abstractText | 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 Muller 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. |
