Abstract
Conversion of astrocytes to neurons (AtN) is a promising potential strategy for the treatment of neurodegenerative diseases. Recent studies have reported that shRNA-, CasRx-, or ASO-mediated Ptbp1 suppression could reprogram resident astrocytes to neurons1–3. However, some groups have disputed the data interpretation of the reported AtN conversion events4–7. These controversies surrounding AtN conversion may due to differences in the astrocyte fate-mapping systems they applied from that in the original study, i.e., recombinant mouse strains with astrocyte specific reporter constructs versus AAV-based labeling systems. Here, we applied two AAV-based tracing systems to label astrocytes with either a GFAP-driven tdTomato reporter (AAV-GFAP::tdTomato) or GFAP-driven HA-tagged Cas13X (AAV-GFAP::Cas13X-NLS-HA-sgPtbp1) and found conflicting observations of AtN conversion in mouse striatum. Our findings indicated that inconsistent AtN outcomes may arise from different fate-mapping systems between AAV and transgenic mice, as well as through use of different reporter proteins. Thus, the complexity of astrocyte labeling systems warrants careful attention when drawing conclusions about whether AtN conversion occurs.
Competing Interest Statement
The authors have declared no competing interest.
