Aging-enhanced accumulation of fibroblasts excludes oligodendrocytes in demyelinated lesions
Lozinski, B. M.; D'Mello, C.; Dong, Y.; Ghorbani, S.; Li, C.; Morch, M.; Moezzi, D.; Jain, R.; Nezhad, P. E.; Ling, C.-C.; Huang, J.; Camara-Lemarroy, C.; Yong, V. W.; Melchor, G. S.
Show abstract
Fibroblast dysregulation contributes to aberrant repair and pathological fibrosis. Emerging evidence suggest that fibroblasts accumulate in lesions following central nervous system injury, but whether and how they influence oligodendrocytes and myeloid cell responses, especially in aging, is uncertain. Here we report that fibroblasts infiltrate the parenchyma of spinal cord white matter (SCWM) lesions after lysolecithin-induced demyelination. Transcriptomic analysis reveals diverse activation states of fibroblasts in lesions and communication networks between fibroblasts, microglia/macrophages and oligodendrocyte precursor cells (OPCs). The invasion of fibroblasts is facilitated by microglia/macrophages, and areas of fibroblast accumulation are devoid of OPCs. Fibroblast density is exacerbated with aging leading to greater fibrosis in lesions. Finally, we found fibroblasts in multiple sclerosis lesions with predicted communication networks between microglia/macrophages and OPCs. These results demonstrate a role of fibroblasts in demyelination-associated neuropathology, which is exacerbated by aging, and highlight the importance of regulating fibroblasts to promote effective CNS repair.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions 97%
- Shared inflammatory glial cell signature after brain injury, revealed by spatial, temporal and cell-type-specific profiling of the murine cerebral cortex 96%
- Genetically perturbed myelin as a risk factor for neuroinflammation-driven axon degeneration 96%
Similar papers in this journal
- Disrupting microglial TGF-β signaling triggers region-specific pathology in the spinal cord 97%
- Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation 96%
- New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination 95%
Similar papers in this journal
- Single Cell Profiling of CD45+ Spinal Cord Cells Reveals Microglial and B Cell Heterogeneity and Crosstalk Following Spinal Cord Injury 96%
- Molecular pathology of acute spinal cord injury in middle-aged mice 96%
- Senolytic treatment depletes microglia and decreases severity of experimental autoimmune encephalomyelitis. 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.