Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling

Lauriane Pous, Sachin S. Deshpande, Suvra Nath, Szilvia Mezey, Subash C. Malik, Sebastian Schildge, Christian Bohrer, Könül Topp, Dietmar Pfeifer, Francisco Fernández-Klett, Soroush Doostkam, Dennis K. Galanakis, Verdon Taylor, Katerina Akassoglou and Christian Schachtrup ()
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Lauriane Pous: University of Freiburg
Sachin S. Deshpande: University of Freiburg
Suvra Nath: University of Freiburg
Szilvia Mezey: University of Freiburg
Subash C. Malik: University of Freiburg
Sebastian Schildge: University of Freiburg
Christian Bohrer: University of Freiburg
Könül Topp: University of Freiburg
Dietmar Pfeifer: University of Freiburg
Francisco Fernández-Klett: Charité – Universitätsmedizin Berlin
Soroush Doostkam: University Medical Center Freiburg, University of Freiburg
Dennis K. Galanakis: State University of New York
Verdon Taylor: University of Basel, Mattenstrasse 28
Katerina Akassoglou: Gladstone Institutes
Christian Schachtrup: University of Freiburg

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14466-y

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