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

Author

Listed:
  • Lauriane Pous

    (University of Freiburg
    University of Freiburg)

  • Sachin S. Deshpande

    (University of Freiburg
    University of Freiburg)

  • Suvra Nath

    (University of Freiburg
    University of Freiburg)

  • Szilvia Mezey

    (University of Freiburg
    University of Freiburg)

  • Subash C. Malik

    (University of Freiburg
    University of Freiburg)

  • Sebastian Schildge

    (University of Freiburg
    University of Freiburg)

  • Christian Bohrer

    (University of Freiburg
    University of Freiburg)

  • Könül Topp

    (University of Freiburg
    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
    University of California San Francisco)

  • Christian Schachtrup

    (University of Freiburg
    University of Freiburg)

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.

Suggested Citation

  • 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, 2020. "Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14466-y
    DOI: 10.1038/s41467-020-14466-y
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    Cited by:

    1. T. M. O’Shea & Y. Ao & S. Wang & A. L. Wollenberg & J. H. Kim & R. A. Ramos Espinoza & A. Czechanski & L. G. Reinholdt & T. J. Deming & M. V. Sofroniew, 2022. "Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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