The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling

Jinyoung Lee, Jung Eun Shin, Bohm Lee, Hyemin Kim, Yewon Jeon, Seung Hyun Ahn, Sung Wook Chi, Yongcheol Cho

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Axon regeneration is regulated by a neuron-intrinsic transcriptional program that is suppressed during development but that can be reactivated following peripheral nerve injury. Here we identify Prom1, which encodes the stem cell marker prominin-1, as a regulator of the axon regeneration program. Prom1 expression is developmentally down-regulated, and the genetic deletion of Prom1 in mice inhibits axon regeneration in dorsal root ganglion (DRG) cultures and in the sciatic nerve, revealing the neuronal role of Prom1 in injury-induced regeneration. Elevating prominin-1 levels in cultured DRG neurons or in mice via adenoassociated virus-mediated gene delivery enhances axon regeneration in vitro and in vivo, allowing outgrowth on an inhibitory substrate. Prom1 overexpression induces the consistent down-regulation of cholesterol metabolism-associated genes and a reduction in cellular cholesterol levels in a Smad pathway-dependent manner, which promotes axonal regrowth. We find that prominin-1 interacts with the type I TGF-β receptor ALK4, and that they synergistically induce phosphorylation of Smad2. These results suggest that Prom1 and cholesterol metabolism pathways are possible therapeutic targets for the promotion of neural recovery after injury.

Original languageEnglish
Pages (from-to)15955-15966
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
Publication statusPublished - 2020 Jul 7

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This work was supported by the National Research Foundation of Korea funded by the Korean Ministry of Science, Information and Communication Technology and Future Planning (Grants 2015R1A5A1009024, to Y.C. and S.W.C and 2016R1A5A2007009, to J.E.S.).

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.


  • Activin
  • Cholesterol metabolism
  • Prominin-1
  • Sciatic nerve injury
  • Smad

ASJC Scopus subject areas

  • General


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