Altered perivascular fibroblast activity precedes ALS disease onset

Autor:	Jennie Olofsson, Peter Lönnerberg, Caroline Ingre, Elena Rodriguez-Vieitez, Inci Sevval Aksoylu, Caroline Mijnsbergen, Manuela Lehmann, Jan H. Veldink, Inti von Gohren Antequera, Albert C. Ludolph, Anna Szczepińska, Stefan Wouters, Mathias Uhlén, Ulf Kläppe, Eleonora Aronica, Hermieneke Vergunst-Bosch, Anna Månberg, Julia Remnestål, Sebastian A. Lewandowski, Lwaki Ebarasi, Peter Nilsson, Aylin Domaniku, Robert A. Harris, Nathan G. Skene, Jasper J. Anink, Joke De Vocht, Eva Hedlund, Annemarie Hübers, Koen Poesen, Philip Van Damme, Marta Trusohamn, Jonathan D. Gilthorpe, Maxim De Schaepdryver, Folkert Sanders
Přispěvatelé:	Pathology, APH - Aging & Later Life, APH - Mental Health, ANS - Cellular & Molecular Mechanisms
Rok vydání:	2021
Předmět:	0301 basic medicine Pathology Transcription Genetic Cell blood [Osteopontin] Disease blood [Amyotrophic Lateral Sclerosis] Superoxide Dismutase-1 0302 clinical medicine Cerebrospinal fluid genetics [Superoxide Dismutase] Medicine SPP1 protein human Perivascular space Amyotrophic lateral sclerosis 11 Medical and Health Sciences physiopathology [Amyotrophic Lateral Sclerosis] General Medicine Prognosis Col6a1 protein human DNA-Binding Proteins genetics [Amyotrophic Lateral Sclerosis] medicine.anatomical_structure Spinal Cord 030220 oncology & carcinogenesis metabolism [Collagen Type VI] Disease Progression metabolism [DNA-Binding Proteins] pathology [Fibroblasts] metabolism [Biomarkers] Genetic Markers pathology [Blood Vessels] medicine.medical_specialty Neurofilament genetics [Collagen Type VI] Immunology Mice Transgenic pathology [Spinal Cord] Collagen Type VI Vascular Remodeling metabolism [RNA Messenger] Article General Biochemistry Genetics and Molecular Biology genetics [RNA Messenger] 03 medical and health sciences ultrastructure [Spinal Cord] Animals Humans ddc:610 RNA Messenger pathology [Amyotrophic Lateral Sclerosis] Fibroblast Superoxide Dismutase business.industry Amyotrophic Lateral Sclerosis Fibroblasts Spinal cord medicine.disease 030104 developmental biology Blood Vessels Osteopontin business Biomarkers
Zdroj:	Nature medicine, 27(4), 640-646. Nature Publishing Group Nat Med Nature medicine 27(4), 640-646 (2021). doi:10.1038/s41591-021-01295-9
ISSN:	1546-170X 1078-8956
Popis:	Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a21731374f1cfb4720d18cbcff7cff41 https://doi.org/10.1038/s41591-021-01295-9 Zobrazit plný text záznamu Full text from SpringerLink