First Author | Li L | Year | 2022 |
Journal | Neuron | Volume | 110 |
Issue | 16 | Pages | 2646-2663.e6 |
PubMed ID | 35952672 | Mgi Jnum | J:348613 |
Mgi Id | MGI:7332700 | Doi | 10.1016/j.neuron.2022.06.022 |
Citation | Li L, et al. (2022) Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes. Neuron 110(16):2646-2663.e6 |
abstractText | Axon regeneration holds great promise for neural repair of CNS axonopathies, including glaucoma. Pten deletion in retinal ganglion cells (RGCs) promotes potent optic nerve regeneration, but only a small population of Pten-null RGCs are actually regenerating RGCs (regRGCs); most surviving RGCs (surRGCs) remain non-regenerative. Here, we developed a strategy to specifically label and purify regRGCs and surRGCs, respectively, from the same Pten-deletion mice after optic nerve crush, in which they differ only in their regeneration capability. Smart-Seq2 single-cell transcriptome analysis revealed novel regeneration-associated genes that significantly promote axon regeneration. The most potent of these, Anxa2, acts synergistically with its ligand tPA in Pten-deletion-induced axon regeneration. Anxa2, its downstream effector ILK, and Mpp1 dramatically protect RGC somata and axons and preserve visual function in a clinically relevant model of glaucoma, demonstrating the exciting potential of this innovative strategy to identify novel effective neural repair candidates. |