Abstract

Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within the SVZ stem cell niche controls NSPC fate. However, extracellular factors within the niche that trigger astrogliogenesis over neurogenesis during CNS disease are unclear. Here, we show that blood-derived fibrinogen is enriched in the SVZ niche following distant cortical brain injury in mice. Fibrinogen inhibited neuronal differentiation in SVZ and hippocampal NSPCs while promoting astrogenesis via activation of the BMP receptor signaling pathway. Genetic and pharmacologic depletion of fibrinogen reduced astrocyte formation within the SVZ after cortical injury, reducing the contribution of SVZ-derived reactive astrocytes to lesion scar formation. We propose that fibrinogen is a regulator of NSPC-derived astrogenesis from the SVZ niche via BMP receptor signaling pathway following injury.

The molecular mechanisms regulating adult neural stem/progenitor cell differentiation following damage of the central nervous system are unclear. Here, the authors show that fibrinogen is a regulator of the adult neural stem/progenitor cell switch from neurogenesis to astrogenesis in a model of stroke

Details

Title
Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling
Author
Pous Lauriane 1 ; Deshpande, Sachin S 1 ; Nath Suvra 1 ; Mezey Szilvia 1 ; Malik, Subash C 1 ; Schildge Sebastian 1 ; Bohrer, Christian 1 ; Topp Könül 1 ; Pfeifer Dietmar 2 ; Fernández-Klett, Francisco 3 ; Doostkam Soroush 4 ; Galanakis, Dennis K 5 ; Taylor, Verdon 6   VIAFID ORCID Logo  ; Akassoglou Katerina 7 ; Schachtrup Christian 8 

1  University of Freiburg, Institute of Anatomy and Cell Biology, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9); University of Freiburg, Faculty of Biology, Freiburg, Germany (GRID:grid.5963.9) 
2  University of Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Freiburg, Germany (GRID:grid.5963.9) 
3  Charité – Universitätsmedizin Berlin, Department of Neuropsychiatry & Laboratory of Molecular Psychiatry, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662) 
4  University Medical Center Freiburg, University of Freiburg, Institute of Neuropathology, Freiburg, Germany (GRID:grid.6363.0) 
5  State University of New York, Department of Pathology, Stony Brook, USA (GRID:grid.36425.36) (ISNI:0000 0001 2216 9681) 
6  University of Basel, Mattenstrasse 28, Department of Biomedicine, Embryology and Stem Cell Biology, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
7  Gladstone Institutes, San Francisco, USA (GRID:grid.249878.8) (ISNI:0000 0004 0572 7110); University of California San Francisco, Department of Neurology, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
8  University of Freiburg, Institute of Anatomy and Cell Biology, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9); University of Freiburg, Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-14466-y
ProQuest document ID
2349174678
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.