Modeling axonal regeneration by changing cytoskeletal dynamics in stem cell-derived motor nerve organoids

Woo Min Seo, Jiyoung Yoon, Ju Hyun Lee, Yunjeong Lee, Hojae Lee, Dongho Geum, Woong Sun, Mi Ryoung Song

Research output: Contribution to journalArticlepeer-review


Oxidative stress triggers axon degeneration and cell death, leading to the development of neurodegenerative diseases. Spinal motor nerves project very long axons, increasing the burden on axonal transport and metabolism. As such, spinal motor nerves are expected to be susceptible to oxidative stress, but model systems for visualizing and investigating acutely degenerating motor axons are limited. In this study, we establish motor nerve organoids from human pluripotent stem cells (hPSCs) with properties similar to those of neuromesodermal progenitors (NMPs), a population of progenitor cells that comprise the caudal spinal cord. Three-dimensional differentiation of organoids efficiently gave rise to mature motor neurons within 18 days. Adherent organoids showed robust axon fascicles and active growth cones under normal conditions. In addition, more homogenous and efficient generation of motor neurons were achieved when organoids were dissociated into individual cells. Hydrogen peroxide-induced oxidative stress resulted in a broad range of signs of axon degeneration including the disappearance of growth cones and neurites, axon retraction, axon fragmentation and bleb formation, and apoptotic cell death, whose severity can be reliably quantifiable in our culture system. Remarkably, cytoskeletal drugs modulating actin or microtubule turnover differentially facilitated axon dynamics and increased axon regenerative potential. Taken together, our motor nerve organoid model could be potentially useful for drug screens evaluating the rearrangement of cytoskeletons in regenerating motor axons.

Original languageEnglish
Article number2082
JournalScientific reports
Issue number1
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Modeling axonal regeneration by changing cytoskeletal dynamics in stem cell-derived motor nerve organoids'. Together they form a unique fingerprint.

Cite this