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

Author:

Pous Lauriane,Deshpande Sachin S.,Nath Suvra,Mezey Szilvia,Malik Subash C.,Schildge Sebastian,Bohrer Christian,Topp Könül,Pfeifer Dietmar,Fernández-Klett Francisco,Doostkam Soroush,Galanakis Dennis K.,Taylor VerdonORCID,Akassoglou Katerina,Schachtrup Christian

Abstract

AbstractNeural 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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