Traumatic brain injury reveals novel cell lineage relationships within the subventricular zone.
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.
The UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Gretchen M
GM
Thomsen
NPI-Semel Institute for Neuroscience & Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Janel E
JE
Le Belle
The UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Jessica A
JA
Harnisch
The UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Whitney S
WS
Mc Donald
The UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
David A
DA
Hovda
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Michael V
MV
Sofroniew
NPI-Semel Institute for Neuroscience & Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: hkornblum@mednet.ucla.edu.
Harley I
HI
Kornblum
The UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: ngharris@mednet.ucla.edu.
Neil G
NG
Harris
D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation / Q000502:physiology; D002552:Cerebral Ventricles / Q000166:cytology*; D020547:Lateral Ventricles / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic