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

Nat Commun. 2020 Jan 31;11(1):630. doi: 10.1038/s41467-020-14466-y.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism*
  • Bone Morphogenetic Proteins / metabolism
  • Fibrinogen / metabolism*
  • Gene Expression Regulation
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Lateral Ventricles / cytology*
  • Lateral Ventricles / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Signal Transduction


  • Bone Morphogenetic Proteins
  • Fibrinogen
  • Bone Morphogenetic Protein Receptors, Type I