Journal Article

Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

Göritz, Christian, Tatarishvili, Jemal, Dias, David O., Ernst, Aurélie, Kelahmetoglu, Yildiz, Huttner, Hagen B., Lindvall, Olle, Jansson, Linda, Brundin, Lou, Banitalebi, Shervin, Holl, Daniel, Frisén, Jonas, Kokaia, Zaal, Amiry-Moghaddam, Mahmood, Kalkitsas, Jannis, Estrada, Cynthia P.

2021

Overview

Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions. Fibrotic scar tissue limits central nervous system regeneration. Here, Dias et al. show that fibrotic scarring is common in mice and humans, following distinct lesions to the adult brain and spinal cord, and derives from a discrete population of GLAST-expressing perivascular cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/51 / 14/1 / 14/19 / 14/32 / 631/378/1687 / 631/378/1687/1825 / 631/378/1689/1666 / 631/378/1689/534 / 64 / 64/60 / Aging - physiology / Animal models / Animals / Astrocytes - pathology / Basic Medicine / Brain / Brain Injuries, Traumatic - pathology / Brain Ischemia - pathology / Brain Neoplasms - pathology / Central nervous system / Central Nervous System - pathology / Cerebral Cortex - pathology / Cicatrix - pathology / Disease Models, Animal / Encephalomyelitis, Autoimmune, Experimental - pathology / Extracellular Matrix - metabolism / Fibroblasts / Fibroblasts - pathology / Fibrosis / Glioblastoma / Glioblastoma - pathology / Head injuries / Humanities and Social Sciences / Humans / Ischemia / Ischemic Stroke - pathology / Lesions / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / Mice / Mice, Inbred C57BL / Mice, Transgenic / multidisciplinary / Multiple sclerosis / Myelin-Oligodendrocyte Glycoprotein / Nervous system / Neurosciences / Neurovetenskaper / Peptide Fragments / Pericytes / Pericytes - pathology / Receptor, Platelet-Derived Growth Factor beta - metabolism / Regeneration / Scars / Science / Science (multidisciplinary) / Spinal cord / Spinal Cord - pathology / Spinal Cord - ultrastructure / Spinal cord injuries / Spinal Cord Injuries - pathology / Stromal cells / Stromal Cells - pathology / Therapeutic targets / Tissues / Traumatic brain injury