Characterization of the ventricular-subventricular stem cell niche during human brain development

Abstract

Human brain development proceeds via a sequentially transforming stem cell population in the ventricular-subventricular zone (V-SVZ). An essential, but understudied, contributor to V-SVZ stem cell niche health is the multi-ciliated ependymal epithelium, which replaces stem cells at the ventricular surface during development. However, reorganization of the V-SVZ stem cell niche and its relationship to ependymogenesis has not been characterized in the human brain. Based on comprehensive comparative spatiotemporal analyses of cytoarchitectural changes along the mouse and human ventricle surface, we uncovered a distinctive stem cell retention pattern in humans as ependymal cells populate the ventricle surface in an occipital-to-frontal wave. During perinatal development ventricle-contacting stem cells are reduced. By 7-months few stem cells are detected, paralleling neurogenesis decline. In adolescence and adulthood, stem cells and neurogenesis are not observed along the lateral wall. Volume, surface area, and curvature of the lateral ventricles all significantly change during fetal development but stabilize after 1-year, corresponding with the wave of ependymogenesis and stem cell reduction. These findings reveal normal human V-SVZ development, highlighting the consequences of disease pathologies such as congenital hydrocephalus.