The microenvironment of the embryonic neural stem cell: Lessons from adult niches? (original) (raw)
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Direct cell–cell contact with the vascular niche maintains quiescent neural stem cells
Nature Cell Biology, 2014
The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculaturesecreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforces quiescence and promotes stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment. Adult stem cells reside in specialized microenvironments, or niches, that maintain them as quiescent, undifferentiated cells to sustain lifelong regeneration 1-3. However, the molecular nature of the signals involved in stem cell maintenance or the cell types from which they originate within the niche remain largely unknown. The subventricular zone (SVZ) is one of the two germinal niches of the adult mammalian brain, where new neurons are continuously produced throughout life. Neurogenesis is initiated from quiescent type-B stem cells that Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
A Stem Cell Niche for Intermediate Progenitor Cells of the Embryonic Cortex
Cerebral Cortex, 2009
The excitatory neurons of the mammalian cerebral cortex arise from asymmetric divisions of radial glial cells in the ventricular zone and symmetric division of intermediate progenitor cells (IPCs) in the subventricular zone (SVZ) of the embryonic cortex. Little is known about the microenvironment in which IPCs divide or whether a stem cell niche exists in the SVZ of the embryonic cortex. Recent evidence suggests that vasculature may provide a niche for adult stem cells but its role in development is less clear. We have investigated the vasculature in the embryonic cortex during neurogenesis and find that IPCs are spatially and temporally associated with blood vessels during cortical development. Intermediate progenitors mimic the pattern of capillaries suggesting patterns of angiogenesis and neurogenesis are coordinated during development. More importantly, we find that IPCs divide near blood vessel branch points suggesting that cerebral vasculature establishes a stem cell niche for intermediate progenitors in the SVZ. These data provide novel evidence for the presence of a neurogenic niche for intermediate progenitors in the embryonic SVZ and suggest blood vessels are important for proper patterning of neurogenesis.
Cerebral Cortex, 2003
The germinal neuroepithelium, or ventricular zone (VZ) of the developing fetal brain, was once thought to transform into the non-germinal ependymal zone of the postnatal and adult brain. Persistence of neural stem cells and neurogenesis throughout postnatal life, however, suggests a continuum between embryonic and adult germinal brain centers. Here, we suggest that developmental changes in anatomy and molecular marker expression in the ventricular walls (the principal germinal centers of the brain) may have misled us into current interpretations of VZ transformation from a germinal to a non-germinal epithelium. We review previous studies and present new data indicating that a germinal layer with characteristics similar to those of the embryonic VZ persists in lateral ventricular walls of the postnatal mouse brain, a region where the adult subventricular zone (SVZ) develops and where neurogenesis persists into adult life. The early postnatal VZ is largely composed of radial glial cell bodies that remain proliferative, display interkinetic nuclear migration and serve as progenitors of new neurons. Ependymal cells then progressively populate the walls of the lateral ventricle but a subpopulation of astrocytes, derived from radial glia, remain in contact with the ventricle lumen, into which they extend a single cilium similar to that found on neuroepithelial cells and radial cells. We propose that a VZ 'compartment' is retained postnatally and that this niche may be essential for stem cell function.
Cerebral Cortex, 2006
Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: the subventricular zone (SVZ), lining the lateral walls of the lateral ventricle, and the subgranular zone of the dentate gyrus. Here we describe a region we will refer to as the subcallosal zone (SCZ). The SCZ is a caudal extension of the SVZ that is no longer associated to an open ventricle. It lies between the hippocampus and the corpus callosum. Cells isolated from the SCZ and cultured as neurospheres behave as neural stem cells in vitro. Using electron and light microscopy, we describe the cell types present in this region and how their organization differs from that of the SVZ. Using retroviral labeling and homotypic-homochronic microtransplantation techniques, we show that the majority of cells born in the SCZ migrate into the corpus callosum to become oligodendrocytes in vivo. This study defines the organization and fate of cells born in a large germinal region of the adult forebrain.
Typical and Atypical Neural Stem Cell Niches
2008
The adult central nervous system (CNS) is a tissue with a low rate of renewal and can be seriously affected by injuries and diseases. The generation of new neural cells, such as neurons and glia, is prevalently restricted to specific CNS areas (niches) deriving from embryonic germinative layers. Continual neurogenesis is sustained by multipotent astro/radial glia-like neural stem/precursor cells (NPCs), which persist within adult CNS niches endowed with molecular/cellular signals capable of regulating their biological features. Multipotent NPCs have less typically been identified in the more spread mammalian CNS parenchyma. Due to their inherent plasticity, NPCs from typical and nontypical CNS germinal areas might therefore concur to nervous system repair upon injury and/or disease. In parallel, the transplantation of NPCs promotes remarkable CNS repair via both cell replacement as well as intrinsic bystander neuroprotective capacities. Strictly depending on when injected into a live host suffering from a CNS disease (e.g., inflammatory vs. degenerative), transplanted NPCs display an extraordinary capacity of finding in vivo the proper way(s) towards certain favourable perivascular sites (atypical niches), where they survive and act as therapeutic weapons trough the interaction with the (micro)environment. The next challenge for the future of (endogenous vs transplanted) stem cell-based therapies will be the development of new protocols for carefully weighting and tightly regulating the different therapeutic alternative mechanisms NPCs may instruct in vivo.
Regulation of Neural Stem Cells in the Human SVZ by Trophic and Morphogenic Factors
Current Signal Transduction Therapy, 2011
The subventricular zone (SVZ), lining the lateral ventricular system, is the largest germinal region in mammals. In there, neural stem cells express markers related to astroglial lineage that give rise to new neurons and oligodendrocytes in vivo. In the adult human brain, in vitro evidence has also shown that astrocytic cells isolated from the SVZ can generate new neurons and oligodendrocytes. These proliferative cells are strongly controlled by a number of signals and molecules that modulate, activate or repress the cell division, renewal, proliferation and fate of neural stem cells. In this review, we summarize the cellular composition of the adult human SVZ (hSVZ) and discuss the increasing evidence showing that some trophic modulators strongly control the function of neural stem cells in the SVZ.