Tracking down regenerative abilities in the adult spinal cord

Published on 17 February 2023

An international collaboration led by scientists at the University of Dundee has discovered one potential roadblock to spinal cord regeneration in humans.

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From left: Professor Kate Storey, Dr Aida Rodrigo Albors and Gail Singer

An international collaboration led by scientists at the University of Dundee has discovered one potential roadblock to spinal cord regeneration in humans.

A spinal cord injury interrupts the circuits that connect the brain and the body. This damage is most often irreversible in humans, resulting in lifelong disability. This contrasts with salamanders like the axolotl which can fully regenerate the spinal cord from resident stem cells, called ependymal cells.

Lead author, Dr Aida Rodrigo Albors explained, “Humans and mice have a similar cell population with latent neural stem cell capabilities. Ependymal cells in mice and humans are, however, much more diverse and we do not know precisely which cells have this ability nor why they are not so good at repairing the injured spinal cord. We reasoned that we may find clues in differences in gene expression between the ependymal cells.”

Aida, supported by research assistant Gail Singer in Professor Kate Storey’s lab in the Division of Molecular, Cell & Developmental Biology in the School of Life Sciences, took advantage of new technology for their research. They used single-cell RNA sequencing, which reveals which genes are expressed in individual cells. This helped them to uncover differences between ependymal cells in the poorly regenerative adult mouse spinal cord. They recently published their findings in the journal Developmental Cell.

Their analyses revealed that some ependymal cells remain in an immature cell state but that these cells eventually mature with age. These findings and the fact that mature cells are very similar to brain ependymal cells (which lack regenerative abilities) suggested that immature ependymal cells may be the ones with regenerative abilities in the adult spinal cord.  

Collaborating with researchers at the Karolinksa Institute in Sweden (Enric Llorens-Bodadilla and Jonas Frisén) they then used mouse models of spinal cord injury to test this. They discovered that injury triggers a reversal of cell maturation that is accompanied by a burst in immature cell proliferation. This response is, however, short-lived and the mature cell state is quickly restored. These findings suggested a model in which mature cells locally repress neural stem cell abilities in their immature neighbours, and that transient maturation reversal releases stem cell behaviour in the injured spinal cord.

Informed by their mouse data, the researchers also investigated ependymal cells in adult human spinal cord and found widespread cell maturation, which may explain the poor regenerative response in humans.

Professor Kate Storey said, “These advances pave the way for manipulation of specific ependymal cell subtypes and rigorous comparison of ependymal cells between regenerative and poorly regenerative species. My lab have made this powerful new resource openly available and hope it will help to inform new strategies to stimulate and direct spinal cord repair.”

This research involved international collaborators from the Karolinksa Institute in Sweden, and the Chan Zuckerberg Biohub in the USA as well as University of Edinburgh and was supported by European Union’s Horizon 2020 Marie Sklodowska-Curie Actions, Wellcome, and the spinal cord research foundation Wings for Life.

Story category Academic collaboration