Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling
Fibrinogen induces neural stem cell differentiation
into astrocytes in the subventricular zone via
BMP signaling
Lauriane Pous1,2, Sachin S. Deshpande1,2, Suvra Nath1,2, Szilvia Mezey1,2, Subash C. Malik1,2, Sebastian Schildge1,2, Christian Bohrer1,2, Könül Topp1,2, Dietmar Pfeifer3, Francisco Fernández-Klett4, Soroush Doostkam5, Dennis K. Galanakis6, Verdon Taylor 7, Katerina Akassoglou8,9 & Christian Schachtrup1,10*
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.