Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling.
Lauriane PousSachin S DeshpandeSuvra NathSzilvia MezeySubash C MalikSebastian SchildgeChristian BohrerKönül ToppDietmar PfeiferFrancisco Fernández-KlettSoroush DoostkamDennis K GalanakisVerdon TaylorKaterina AkassoglouChristian SchachtrupPublished in: Nature communications (2020)
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.
Keyphrases
- stem cells
- brain injury
- cerebral ischemia
- signaling pathway
- mesenchymal stem cells
- subarachnoid hemorrhage
- blood brain barrier
- epithelial mesenchymal transition
- pi k akt
- lymph node
- gene expression
- oxidative stress
- induced apoptosis
- skeletal muscle
- cell proliferation
- resting state
- cell therapy
- functional connectivity
- insulin resistance