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

David O. Dias, Jannis Kalkitsas, Yildiz Kelahmetoglu, Cynthia P. Estrada, Jemal Tatarishvili, Daniel Holl, Linda Jansson, Shervin Banitalebi, Mahmood Amiry-Moghaddam, Aurélie Ernst, Hagen B. Huttner, Zaal Kokaia, Olle Lindvall, Lou Brundin, Jonas Frisén and Christian Göritz ()
Additional contact information
David O. Dias: Karolinska Institutet
Jannis Kalkitsas: Karolinska Institutet
Yildiz Kelahmetoglu: Karolinska Institutet
Cynthia P. Estrada: Karolinska University Hospital
Jemal Tatarishvili: Lund Stem Cell Center, Lund University
Daniel Holl: Karolinska Institutet
Linda Jansson: Lund Stem Cell Center, Lund University
Shervin Banitalebi: Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo
Mahmood Amiry-Moghaddam: Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo
Aurélie Ernst: Karolinska Institutet
Hagen B. Huttner: University Hospital Erlangen
Zaal Kokaia: Lund Stem Cell Center, Lund University
Olle Lindvall: Lund Stem Cell Center, Lund University
Lou Brundin: Karolinska University Hospital
Jonas Frisén: Karolinska Institutet
Christian Göritz: Karolinska Institutet

Nature Communications, 2021, vol. 12, issue 1, 1-24

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25585-5

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