Turning astrocytes into neurons: a dispute

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Hao Qian, Xiang-Dong Fu, Don Cleveland and colleagues (University of California San Diego, Nature) and Haibo Zhou, Hui Yang and colleagues (Institute of Neuroscience, Shanghai; Cell, CasRx version). Challenges came from Wei Chen, Mingtao Li and colleagues (Sun Yat-sen University, eLife 2022), Chun-Li Zhang's group (Wang et al., Cell 2021), Seth Blackshaw's group (Hoang et al., Nature 2023) and others.

What happened

Astrocytes are abundant support cells that stay alive when neurons die, so converting them in place would need no transplant. Qian et al. (Nature 2020;582:550–556) reported that depleting PTB (PTBP1) converted mouse and human astrocytes into neurons, and in a chemically induced mouse model restored striatal dopamine and rescued motor deficits. (A blog summary gives about a third of lost nigral neurons restored and striatal dopamine at about 65% of normal versus about 25% in controls; I could not check these numbers in the paper.) The paper has an author correction (Nature 2020;584:E17, 29 Jul 2020: the Fig. 5e labels "Empty" and "shPTB" had been swapped, and an affiliation was added; read at nature.com, checked 23 Oct 2026). Short-term antisense oligonucleotides gave similar results. Zhou et al. (Cell 2020;181:590–603) reported a CRISPR-CasRx version, which turned retinal glia into retinal ganglion cells and induced neurons with dopaminergic features in the striatum of a Parkinson's mouse model.

Doubts started at once: Ole Isacson noted that viral Cre leakage could label existing neurons. Wang et al. (Cell 2021;184:5465) used lineage tracing to revisit conversion. Chen et al. found that dopamine neurons seen after PTBP1 knockdown lacked the genetic tag marking astrocyte origin, so were not converted astrocytes, and that PTBP1 suppression did not generate neurons or improve motor deficits. Hoang et al. (Nature 2023;618:E1–E7, a Matters Arising comment) found that Ptbp1 deletion did not induce astrocyte-to-neuron conversion; Qian's group replied in the same issue (E8–E13) and defended its result. Xie et al. (eBioMedicine 2023) found AAV leakage into neurons was common and, with tools that reduce it, Neurod1 did not convert traced glia. Zhang et al. (eLife 2025) deleted PTBP1 in lineage-traced adult astrocytes and found no widespread neurons and no neuron-like splicing.

Why it moved us toward a cure

Skin cells had already been converted straight into dopamine neurons in the lab (landmark 214). It showed how to test in-place regeneration properly, and why: a cure by repair needs real new neurons, not labelled old ones. Standards for lineage tracing now shape the field.

Outcome

Open and contested, leaning against the original claim: four independent lineage-tracing studies (2021–2025) found no conversion, while the original authors maintain theirs. No primate data. The 2022 commentary says PTBP1 still merits study but is "not the sole gatekeeper". If the field settles against it, this would become a dead end; I kept it open because the original papers are neither retracted nor withdrawn.

Sources

• Qian et al., Nature 2020;582:550–556, DOI 10.1038/s41586-020-2388-4 · numbers via blog summary
• Zhou et al., Cell 2020;181:590–603, DOI 10.1016/j.cell.2020.03.024 · Alzforum
• Hoang et al., Nature 2023, DOI 10.1038/s41586-023-06066-9 and Hao et al. reply, DOI 10.1038/s41586-023-06067-8
• Chen et al., eLife 2022;11:e75636, DOI 10.7554/eLife.75636
• Zhang et al., eLife 2025;14:RP107683, DOI 10.7554/eLife.107683 · Isacson comment on Qian
• Cooper and Berninger, eLife 2022;11:e80232 (on Chen et al.) · Wang et al., Cell 2021 record
• Xie et al., eBioMedicine 2023;90:104531
• Not yet verified: the Qian numbers from the paper (secondary summary only); funders; the full texts of the 2023 exchange; any resolution beyond the 2025 eLife paper.