Circulating Platelets Modulate Oligodendrocyte Progenitor Cell Differentiation During Remyelination

  1. Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
  2. Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile
  3. Wellcome-MRC Cambridge Stem Cell Institute & Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
  4. Translational Regenerative Neurobiology Group, Molecular and Integrative Biosciences Research Program (MIBS), Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland
  5. Institute of Animal Science, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile
  6. Department of Haematology and NHS Blood and Transplant, University of Cambridge, Cambridge, UK
  7. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria
  8. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
  9. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
  10. Laboratory of Cellular Pathology, Institute of Anatomy, Histology & Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
  11. Institute of Pharmacy, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile
  12. Laboratory of Developmental Biology, Department of Biology, University of Patras, 26504 Patras, Greece

Peer review process

Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, public reviews, and a response from the authors (if available).

Read more about eLife’s peer review process.

Editors

  • Reviewing Editor
    Vitaly Ryu
    Icahn School of Medicine at Mount Sinai, New York, United States of America
  • Senior Editor
    Timothy Behrens
    University of Oxford, Oxford, United Kingdom

Reviewer #1 (Public Review):

Summary:
The authors have studied the effects of platelets in OPC biology and remyelination. For this, they used mutant mice with lower levels of platelets as a demyelinating/remyelinating scenario, as well as in a model with large numbers of circulating platelets.

Strengths:
-The work is very focused, with defined objectives.
-The work is properly done.

Weaknesses:
-There is no clear effect on a single cell type and/or mechanism involved.

Reviewer #2 (Public Review):

Summary:
This paper examined whether circulating platelets regulate oligodendrocyte progenitor cell (OPC) differentiation for the link with multiple sclerosis (MS). They identified that the interaction with platelets enhances OPC differentiation although persistent contact inhibits the process in the long-term. The mouse model with increased platelet levels in the blood reduced mature oligodendrocytes, while how platelets might regulate OPC differentiation is not clear yet.

Strengths:
The use of both partial platelet depletion and thrombocytosis mouse models gives in vivo evidence. The presentation of platelet accumulation in a time-course manner is rigorous. The in vitro co-culture model tested the role of platelets in OPC differentiation, which was supportive of in vivo observations.

Weaknesses:
How platelets regulate OPC differentiation is not clear. What the significance of platelets is in MS progression is not clear.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation