Circulating Platelets Modulate Oligodendrocyte Progenitor Cell Differentiation During Remyelination

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.