Molecular and functional heterogeneity in dorsal and ventral oligodendrocyte progenitor cells of the mouse forebrain in response to DNA damage

Enrica Boda (), Martina Lorenzati, Roberta Parolisi, Brian Harding, Gianmarco Pallavicini, Luca Bonfanti, Amanda Moccia, Stephanie Bielas, Ferdinando Di Cunto and Annalisa Buffo
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Enrica Boda: University of Turin
Martina Lorenzati: University of Turin
Roberta Parolisi: University of Turin
Brian Harding: University of Pennsylvania and Children’s Hospital of Philadelphia
Gianmarco Pallavicini: University of Turin
Luca Bonfanti: University of Turin
Amanda Moccia: University of Michigan
Stephanie Bielas: University of Michigan
Ferdinando Di Cunto: University of Turin
Annalisa Buffo: University of Turin

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract In the developing mouse forebrain, temporally distinct waves of oligodendrocyte progenitor cells (OPCs) arise from different germinal zones and eventually populate either dorsal or ventral regions, where they present as transcriptionally and functionally equivalent cells. Despite that, developmental heterogeneity influences adult OPC responses upon demyelination. Here we show that accumulation of DNA damage due to ablation of citron-kinase or cisplatin treatment cell-autonomously disrupts OPC fate, resulting in cell death and senescence in the dorsal and ventral subsets, respectively. Such alternative fates are associated with distinct developmental origins of OPCs, and with a different activation of NRF2-mediated anti-oxidant responses. These data indicate that, upon injury, dorsal and ventral OPC subsets show functional and molecular diversity that can make them differentially vulnerable to pathological conditions associated with DNA damage.

Date: 2022
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DOI: 10.1038/s41467-022-30010-6

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