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Identification of regenerative processes in neonatal spinal cord injury in the opossum (Monodelphis domestica): A transcriptomic study
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, New Mexico, USA.ORCID-id: 0000-0003-0619-4777
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2021 (Engelska)Ingår i: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 529, nr 5, s. 969-986Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

This study investigates the response to spinal cord injury in the gray short‐tailed opossum (Monodelphis domestica). In opossums spinal injury early in development results in spontaneous axon growth through the injury, but this regenerative potential diminishes with maturity until it is lost entirely. The mechanisms underlying this regeneration remain unknown. RNA sequencing was used to identify differential gene expression in regenerating (SCI at postnatal Day 7, P7SCI) and nonregenerating (SCI at Day 28, P28SCI) cords +1d, +3d, and +7d after complete spinal transection, compared to age‐matched controls. Genes showing significant differential expression (log2FC ≥ 1, Padj ≤ 0.05) were used for downstream analysis. Across all time‐points 233 genes altered expression after P7SCI, and 472 genes altered expression after P28SCI. One hundred and forty‐seven genes altered expression in both injury ages (63% of P7SCI data set). The majority of changes were gene upregulations. Gene ontology overrepresentation analysis in P7SCI gene‐sets showed significant overrepresentations only in immune‐associated categories, while P28SCI gene‐sets showed overrepresentations in these same immune categories, along with other categories such as “cell proliferation,” “cell adhesion,” and “apoptosis.” Cell‐type–association analysis suggested that, regardless of injury age, injury‐associated gene transcripts were most strongly associated with microglia and endothelial cells, with strikingly fewer astrocyte, oligodendrocyte and neuron‐related genes, the notable exception being a cluster of mostly downregulated oligodendrocyte‐associated genes in the P7SCI + 7d gene‐set. Our findings demonstrate a more complex transcriptomic response in nonregenerating cords, suggesting a strong influence of non‐neuronal cells in the outcome after injury and providing the largest survey yet of the transcriptomic changes occurring after SCI in this model.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2021. Vol. 529, nr 5, s. 969-986
Nyckelord [en]
axon regeneration, GO category overrepresentation, gray short-tailed opossum (Monodelphis domestica), RNA sequencing, spinal cord injury
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-175099DOI: 10.1002/cne.24994ISI: 000563974800001PubMedID: 32710567Scopus ID: 2-s2.0-85088876133OAI: oai:DiVA.org:umu-175099DiVA, id: diva2:1468169
Forskningsfinansiär
NIH (National Institute of Health)Tillgänglig från: 2020-09-17 Skapad: 2020-09-17 Senast uppdaterad: 2022-10-31Bibliografiskt granskad

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Wheaton, Benjamin J.

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