Traumatic brain injury reveals novel cell lineage relationships within the subventricular zone

•Expansion of the SVZ niche after TBI is mainly due to Mash1 transit amplifying cells.•EGFR + progenitors decrease proliferation and can become GFAP + after injury.•TBI increases the number of EGFR +/GFAP + SVZ stem cells without proliferation.•These data indicate the likelihood of an altered lineage progression after TBI.

The acute response of the rodent subventricular zone (SVZ) to traumatic brain injury (TBI) involves a physical expansion through increased cell proliferation. However, the cellular underpinnings of these changes are not well understood. Our analyses have revealed that there are two distinct transit-amplifying cell populations that respond in opposite ways to injury. Mash1 + transit-amplifying cells are the primary SVZ cell type that is stimulated to divide following TBI. In contrast, the EGFR + population, which has been considered to be a functionally equivalent progenitor population to Mash1 + cells in the uninjured brain, becomes significantly less proliferative after injury. Although normally quiescent GFAP + stem cells are stimulated to divide in SVZ ablation models, we found that the GFAP + stem cells do not divide more after TBI. We found, instead, that TBI results in increased numbers of GFAP +/EGFR + stem cells via non-proliferative means—potentially through the dedifferentiation of progenitor cells. EGFR + progenitors from injured brains only were competent to revert to a stem cell state following brief exposure to growth factors. Thus, our results demonstrate previously unknown changes in lineage relationships that differ from conventional models and likely reflect an adaptive response of the SVZ to maintain endogenous brain repair after TBI.

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