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 surface of the ventricle in an occipital-to-frontal wave. During perinatal development, ventricle-contacting stem cells are reduced. By 7 months few stem cells are detected, paralleling the decline in neurogenesis. 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.

GemC1 is a critical switch for neural stem cell generation in the postnatal brain

“…As Geminin was previously shown to be implicated in stem cell self-renewal and differentiating decisions (Karamitros et al, 2015;Spella et al, 2011), antagonistic roles for Geminin and GemC1 in determining the ependymal cell lineage are likely. Although the human genetic findings we provide will require further validation by sequencing other congenital hydrocephalus patients, the fact that ependymogenesis in mice and humans shares many common characteristics (Coletti et al, 2018;Pressler & Auvin, 2013), suggests that the mechanism defined here in mice may be operative in some forms of human congenital hydrocephalus.…”

Developmental dynamics of neurogenesis and gliogenesis in the postnatal mammalian brain in health and disease: Historical and future perspectives

“…Since then, there have been a number of studies that support both ideas (Kaur, Rathnasamy, & Ling, 2016;Luo et al, 2015;Mirzadeh et al, 2008;Shah et al, 2018). At the end, it has turned out that the soma and/or apical processes of NSCs actually reside in both the ependymal and subependymal regions, and, thus, cells with a NSCs capacity and typical ependymal cells with motile multi cilia coexist in the ependymal layer (Abdelhamed et al, 2018;Coletti et al, 2018;Del Bigio, 2010;Guo et al, 2010;S. H. Kang et al, 2010;Mirzadeh et al, 2008;Paez-Gonzalez et al, 2011;Tripathi et al, 2010).…”

“…Ependymal cells form a single-cell-layer epithelium that separates the brain parenchyma from the LV and other ventricular systems (Del Bigio, 2010). Although ependymal cells lining the LV have long been thought to develop postnatally, recent studies have demonstrated that they start to emerge as early as E13 in mice near the posterior edge of the LV and progressively spread over the entire LV during late embryonic and early postnatal stages (Abdelhamed et al, 2018;Coletti et al, 2018). Importantly, while embryonic RGCs in the germinal zone transform into postnatal NSCs in the VZ-SVZ region, they also generate ependymal cells in the same region (Paez-Gonzalez et al, 2011).…”

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

“…Hippocampus and cerebellum neurons seem very sensitive and hypoxia-intolerant [26], whereas neural stem-cells require hypoxic niches to remain in an undifferentiated state and maintain their pluripotency [34]. The physiological hypoxic niches are notably located in the sub-ventricular zone (SVZ) along the lateral walls of the lateral ventricles, the major site of post-natal continuous neurogenesis [23,34,35]. Controversial studies have investigated this SVZ niche as a region originating glioma stem cells [36,37].…”

“…However, growing evidence suggests that HIF-1α and HIF-2α are differentially regulated in a time-dependent manner. In fact, HIF-1α is dedicated to acute hypoxia, whereas HIF-2α seems to be expressed during chronic phase of hypoxia to maintain immature cells and probably pHGG stem cell niches [27,29,35,53,54]. Their hyperexpressions are quite frequent in DIPG and pHGG cohorts.…”