Abstract
Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1α1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1α1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1α1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Analysis of Variance
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Animals
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Antigens / genetics
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Blood Vessels / metabolism
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Blood Vessels / pathology
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CD13 Antigens / metabolism
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Cell Count
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Cicatrix / etiology*
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Collagen Type I, alpha 1 Chain
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Disease Models, Animal
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Disease Progression
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Female
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Fibroblasts / pathology*
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Gene Expression Regulation / genetics
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins / genetics
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Lectins
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Leukocyte Common Antigens
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Pericytes / metabolism
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Pericytes / pathology*
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Piperidines / metabolism
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Proteoglycans / genetics
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Receptor, Platelet-Derived Growth Factor beta / metabolism
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Spinal Cord Injuries / complications*
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Spinal Cord Injuries / pathology
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Time Factors
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Uracil / analogs & derivatives
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Uracil / metabolism
Substances
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Antigens
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Collagen Type I
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Collagen Type I, alpha 1 Chain
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Glial Fibrillary Acidic Protein
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Lectins
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Piperidines
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Proteoglycans
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chondroitin sulfate proteoglycan 4
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Green Fluorescent Proteins
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Uracil
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Receptor, Platelet-Derived Growth Factor beta
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Leukocyte Common Antigens
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CD13 Antigens
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alogliptin