Dissecting the evolving cellular landscape of a remyelinating microenvironment
Open accessAbstract
Demyelination, or the loss of myelin in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and occurs in various forms of CNS injury and neurodegenerative diseases. The regeneration of myelin, or remyelination, occurs spontaneously following demyelination. The lysophosphatidylcholine (LPC)-induced focal demyelination model enables investigations into the mechanisms of remyelination, providing insight into the molecular basis underlying an evolving remyelinating microenvironment over a tractable time course. Here, we present a detailed analysis using high-resolution single nucleus RNA sequencing to investigate gene expression dynamics across multiple cell populations involved in the remyelination process. We examine three specific time points following focal demyelinating injury in mice, and by delineating activation states within the heterogeneous cell populations of demyelinated lesions, we highlight changes in gene expression within subclusters of each cell population from the early stages of injury response to the initiation and maintenance of remyelination. Our findings reveal how shifts in microglial, astrocytic and fibroblast activities within lesions are associated with efficient oligodendrocyte differentiation during remyelination.
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Reanalyzed snRNA-sequencing data show increased myeloid cell expression in the lesion of many anti-apoptotic genes that D/Q targets.
“our reanalyzed snRNA-sequencing data31 shows increased myeloid cell expression in the lesion of many of the anti-apoptotic genes D/Q targets (Supplementary Fig. 7g).”
From Senescent-like microglia limit remyelination through the senescence associated secretory phenotype (2025) · cites this paper as [31]
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Senescent-like microglia limit remyelination through the senescence associated secretory phenotype
Gross, P. S., Durán-Laforet, V., Ho, L. T., Melchor, G. S., Zia, S., Manavi, Z., Barclay, W. E., Lee, S. H., Shults, N., Selva, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57632-w · Cited by 62 · see citing works
“D/Q is currently being used in several clinical trials to deplete senescent cells 46,50 , and our reanalyzed snRNA-sequencing data 31 shows increased myeloid cell expression in the lesion of many of the anti-apoptotic genes D/Q targets ( Supplementary Fig.”
InfluentialSelf-citation
- Authors
- Melchor, G. S., Baydyuk, M., Manavi, Z., Hu, J., & Huang, J. K.
- Affiliations
- Georgetown University (US)
- Corresponding author
- Huang, Jeffrey K.
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2024-12-25
- PMC
- PMC11703248
- OpenAlex
- W4405781387
- Cited by
- 3
- References
- 20
- Citations by year
- 2026: 1 · 2025: 2
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- remyelination, demyelination, multiple sclerosis, single-nucleus RNA sequencing, demyelinating lesions, microglia, astrocytes, fibroblasts, oligodendrocyte differentiation, gene expression dynamics, central nervous system injury
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