Inflammation-induced epigenetic memory restores oligodendrocyte progenitor cell regenerative capacity in the aged central nervous system

Cabeza-Fernandez, S.; Ninerola, S.; Armengol-Gomis, A.; Paraiso-Luna, J.; Casillas-Bajo, A.; Gomez-Sanchez, J. A.; Cabedo, H.; Barco, A.; de la Fuente, A. G.

doi:10.64898/2026.05.11.724385

bioRxiv · 10.64898/2026.05.11.724385

Inflammation-induced epigenetic memory restores oligodendrocyte progenitor cell regenerative capacity in the aged central nervous system

Cabeza-Fernandez, S.·Ninerola, S.·Armengol-Gomis, A.·Paraiso-Luna, J.·Casillas-Bajo, A.·Gomez-Sanchez, J. A.·Cabedo, H.·Barco, A.·de la Fuente, A. G.

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Abstract

Although remyelination, a central nervous system (CNS) regenerative process mediated by oligodendrocyte progenitor cells (OPCs), takes place in an inflammatory environment the long-term impact of inflammation on OPC remyelination capacity remains unclear. Here, we studied the short- and long-term impact of systemic inflammation on adult OPCs to assess whether transient inflammation triggers enduring chromatin remodelling indicative of inflammatory memory in OPCs. We observed long-lasting epigenetic modifications in response to both lipopolyssaccharide (LPS) and polyinosinic:polycytidylic acid (Poly(I:C)), but only LPS induced a tolerance-like memory. LPS-mediated tolerance-like memory enhanced OPC differentiation after demyelination in aged mice, reducing axonal damage. Our findings reveal OPC epigenetic memory of inflammation as a mechanism by which adult OPCs adapt to inflammatory challenges, which could be harnessed to reduce neuroinflammation and enhance remyelination efficiency in ageing and neurodegenerative diseases.

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Cabeza-Fernandez, S., Ninerola, S., Armengol-Gomis, A., Paraiso-Luna, J., Casillas-Bajo, A., Gomez-Sanchez, J. A., Cabedo, H., Barco, A., de la Fuente, A. G.. 2026-05-13. Inflammation-induced epigenetic memory restores oligodendrocyte progenitor cell regenerative capacity in the aged central nervous system. https://doi.org/10.64898/2026.05.11.724385

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