Expanding gliogenesis

doi:10.1126/science.abj1139

GSTDTAP > 气候变化

DOI	10.1126/science.abj1139
	Expanding gliogenesis
	Katherine T. Baldwin; Debra L. Silver
	2021-06-11
发表期刊	Science
出版年	2021
英文摘要	The adult mammalian brain retains the capacity to generate new neurons and glia, a feature that is important for learning, memory, and response to injury ([ 1 ][1]). Neural stem cells (NSCs) in germinal regions of the adult brain, such as the ventricular-subventricular zone (V-SVZ) and the dentate gyrus of the hippocampus, are a major source of new neurons and glia ([ 1 ][1]). Glia, including astrocytes, oligodendrocytes, ependymal cells, and microglia, are non-neuronal cells that play critical roles in brain function. Although the neurogenic functions of stem cells in the adult V-SVZ have been studied extensively, their gliogenic properties are less well understood. On page 1205 of this issue, Delgado et al. ([ 2 ][2]) reveal previously undescribed gliogenic origins and glial cell types in the adult mouse brain. This discovery suggests that adult gliogenesis is more widespread than previously thought, laying the groundwork for potential regenerative therapies. During development, stem cells rapidly divide; however, in adult tissues, they are mostly quiescent ([ 3 ][3]). The largest population of NSCs in the adult mammalian brain resides in the V-SVZ, lining the lateral and septal walls of the lateral ventricle. They are maintained in a dormant state by both intrinsic factors and extrinsic cues from the surrounding niche, which is composed of ventricular cerebrospinal fluid (CSF) derived from the choroid plexus, and vasculature, ependymal cells, and neurons ([ 1 ][1]). The spatial location of NSCs confers their identity, with different regions of the V-SVZ generating distinct cell types ([ 4 ][4]). NSCs lining the lateral and septal walls generate interneurons that populate the olfactory bulb, whereas those in the dorsal-lateral V-SVZ generate oligodendrocytes ([ 5 ][5], [ 6 ][6]). Although both NSCs and astrocytes share similar morphology and express glial fibrillary acidic protein (GFAP), V-SVZ NSCs do not normally generate astrocytes, although they produce reactive astrocytes after stroke ([ 7 ][7]). Hence, the extent of gliogenesis, including astrocyte generation, in the adult V-SVZ is unknown. Questions remain whether distinct spatial origins exist in the V-SVZ and what intrinsic and extrinsic factors control NSC activity and potency. Delgado et al. sought to identify regulators of NSC quiescence. Platelet-derived growth factor receptor–β (PDGFRβ) is enriched in quiescent NSCs ([ 8 ][8]), and the authors found that genetic deletion of Pdgfrb from adult NSCs released them from quiescence, which concomitantly increased NSC progeny, including transit amplifying cells, olfactory bulb neurons, and oligodendrocytes. Notably, PDGFDD, a PDGFRβ-specific ligand, was detected in the CSF. Thus, PDGF signaling from the CSF maintains NSCs in a quiescent state and in its absence, NSCs divide. Serendipitously, after release of NSCs from quiescence, Delgado et al. discovered previously unknown glial cell types (see the figure). Upon PDGFRβ ablation, the authors observed morphologically distinct radial GFAP-expressing cells, including a new cell type on the V-SVZ septal wall, called gorditas. Release from quiescence also increased astrocyte numbers in the septum. Additionally, Delgado et al. found that these gliogenic NSCs are active in wild-type mice following brain injury. Indeed, after a focal demyelinating injury to the corpus callosum, both gorditas and oligodendrocyte-lineage cell numbers increased in different subregions of the V-SVZ. This suggests that these glial cells may function in injury repair. The authors also discovered an oligodendrocyte precursor cell (OPC) within the ventricles, both after NSC release from quiescence through Pdgfrb deletion and in wild-type uninjured brains. Canonical OPCs are found throughout the brain parenchyma and generate oligodendrocytes to promote myelin formation in the developing and adult brain ([ 9 ][9]). The intraventricular OPCs characterized by Delgado et al. expressed conventional OPC markers, including PDGFRα, and their emergence during the first postnatal week corresponds to increased expression of the ligand PDGFAA in the CSF. Many intraventricular OPCs were adjacent to or partially enwrapping supraependymal axons, extending from neurons in other brain regions. Parenchymal OPCs functionally communicate with neurons by receiving depolarizing synaptic inputs from axons ([ 9 ][9]). Whether intraventricular OPCs also communicate with supraependymal axons remains to be explored, as does the contribution of this new cell type to myelin repair. Nevertheless, the positioning of intraventricular OPCs suggests a potentially powerful role for these cells in integrating and dynamically responding to signals from the CSF and other brain regions. ![Figure][10] Gliogenic domains in the adult brain Neural stem cells (NSCs) in the mouse adult ventricular-subventricular zone (V-SVZ), which lines the lateral and septal walls of the lateral ventricle (LV), are maintained in a quiescent state by intrinsic and extrinsic cues, including platelet-derived growth factor (PDGF) signaling and other unknown factors. GRAPHIC: C. BICKEL/ SCIENCE Together, the findings of Delgado et al. advance the understanding of glial cell heterogeneity. Once viewed as largely homogeneous populations, recent studies emphasize the high degree of molecular and functional heterogeneity that exists in glial cell populations, including OPCs ([ 10 ][11]) and astrocytes ([ 11 ][12], [ 12 ][13]). The identification of intraventricular OPCs and different GFAP-positive radial cells adds fuel to this ongoing investigation. Furthermore, the findings of Delgado et al. may provide a new platform for investigating mechanisms of astrocyte maturation, a poorly understood process that is critical for normal brain development and function. The discovery of new gliogenic domains in the adult brain opens many new lines of inquiry. There are likely additional pathways beyond PDGFRβ signaling that control NSC quiescence and gliogenic potency. Indeed, the observation that different ventricular domains harbor distinct gliogenic precursors indicates that cues from local niches are important. Transcriptome datasets of NSCs ([ 8 ][8], [ 12 ][13]), as well as recent discoveries of signaling molecules within the V-SVZ niche ([ 1 ][1], [ 13 ][14]), provide both intrinsic and extrinsic candidates for future investigation. Subsequent studies will also elucidate the extent to which common mechanisms control adult neurogenesis and gliogenesis. The discovery of previously unknown glial cell types also raises questions about the ontogenetic relationship between diverse GFAP-positive progenitors. Employing detailed in vivo lineage tracing, live imaging, and single-cell analyses will further flesh out relationships between anatomical position, birth date, and cell fate. Whereas glia, including astrocytes and oligodendrocytes, are produced in adult mice, gliogenesis in humans is less well defined. In the human brain, particularly in the hippocampus, the extent of adult neurogenesis has been debated, with some studies showing that proliferating stem cells decrease into adulthood, whereas others suggest that some adult neurogenesis is retained ([ 14 ][15]). Determining the extent of gliogenesis in the adult human brain will rely on similar studies with primary tissue, and perhaps the use of other models, such as human brain organoids. Beyond injury, adult gliogenesis in humans may contribute to homeostatic brain functions such as memory and learning. Thus, future studies of NSCs may give therapeutic insights toward enhancing brain resilience, function, and improved brain repair. 1. [↵][16]1. K. Obernier, 2. A. Alvarez-Buylla , Development 146, dev156059 (2019). [OpenUrl][17][Abstract/FREE Full Text][18] 2. [↵][19]1. A. C. Delgado et al ., Science 372, 1205 (2021). [OpenUrl][20][Abstract/FREE Full Text][21] 3. [↵][22]1. C. M. Morshead et al ., Neuron 13, 1071 (1994). 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领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/329902
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Katherine T. Baldwin,Debra L. Silver. Expanding gliogenesis[J]. Science,2021.
APA	Katherine T. Baldwin,&Debra L. Silver.(2021).Expanding gliogenesis.Science.
MLA	Katherine T. Baldwin,et al."Expanding gliogenesis".Science (2021).