Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone.

In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches-the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of Hdac8 in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.

Generation of immunocompetent somatic glioblastoma mouse models through in situ transformation of subventricular zone neural stem cells.

Disease-relevant in vivo tumor models are essential tools for both discovery and translational research. Here, we describe a highly genetically tractable technique for generating immunocompetent somatic glioblastoma (GBM) mouse models using piggyBac transposition and CRISPR-Cas9-mediated gene editing in wild-type mice. We describe steps to deliver plasmids into subventricular zone endogenous neural stem cells by injection and electroporation, leading to the development of adult tumors that closely recapitulate the histopathological, molecular, and cellular features of human GBM. For complete details on the use and execution of this protocol, please refer to Garcia-Diaz et al.1.

[New Preoperative Simulations for the Future of Hydrocephalus Surgery].

Ventricular puncture is a basic procedure that neurosurgeons learn in the early stages of their careers and is also performed in ventricular drainage and neuroendoscopic surgery. However, few neurosurgeons are confident in their ability to insert and place a ventricular catheter in the optimal position for ventriculoperitoneal(VP)shunting in a single pass. Even experienced neurosurgical consultants confident in difficult microsurgical procedures are uncomfortable with ventricular catheter placement in VP shunting. Moreover, many neurosurgeons believe that they will never perform a ventricular puncture from the posterior horn of the lateral ventricles. The reason for thinking that ventricular puncture via the anterior horn is safer and more accurate compared with the posterior approach is because the anterior approach can use facial landmarks such as eyes, nose, and ears. However, even with the anterior approach in VP shunting, it is more difficult than with ventricular drainage or neuroendoscopic surgery to achieve accurate placement owing to head rotation, and the success rate has been reported to be as high as 50%. In this article, I introduced "fool proof," which uses preoperative simulation to place a ventricular catheter in the optimal position according to the size and shape of each patient's head and ventricles. The first choice for VP shunting is the right parieto-occipital approach with a posterior horn puncture from Frazier's Point and, for L-P shunting, a paramedian puncture from the 2/3 or 3/4 lumbar interspace.

Toward a better understanding of how a gyrified brain develops.

The size and shape of the cerebral cortex have changed dramatically across evolution. For some species, the cortex remains smooth (lissencephalic) throughout their lifetime, while for other species, including humans and other primates, the cortex increases substantially in size and becomes folded (gyrencephalic). A folded cortex boasts substantially increased surface area, cortical thickness, and neuronal density, and it is therefore associated with higher-order cognitive abilities. The mechanisms that drive gyrification in some species, while others remain lissencephalic despite many shared neurodevelopmental features, have been a topic of investigation for many decades, giving rise to multiple perspectives of how the gyrified cerebral cortex acquires its unique shape. Recently, a structurally unique germinal layer, known as the outer subventricular zone, and the specialized cell type that populates it, called basal radial glial cells, were identified, and these have been shown to be indispensable for cortical expansion and folding. Transcriptional analyses and gene manipulation models have provided an invaluable insight into many of the key cellular and genetic drivers of gyrification. However, the degree to which certain biomechanical, genetic, and cellular processes drive gyrification remains under investigation. This review considers the key aspects of cerebral expansion and folding that have been identified to date and how theories of gyrification have evolved to incorporate this new knowledge.

Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1+ ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.

Validation of a methylation-based signature for subventricular zone involvement in glioblastoma.

PURPOSE: Glioblastomas (GBM) with subventricular zone (SVZ) contact have previously been associated with a specific epigenetic fingerprint. We aim to validate a reported bulk methylation signature to determine SVZ contact. METHODS: Methylation array analysis was performed on IDHwt GBM patients treated at our institution. The v11b4 classifier was used to ensure the inclusion of only receptor tyrosine kinase (RTK) I, II, and mesenchymal (MES) subtypes. Methylation-based assignment (SVZM ±) was performed using hierarchical cluster analysis. Magnetic resonance imaging (MRI) (T1ce) was independently reviewed for SVZ contact by three experienced readers. RESULTS: Sixty-five of 70 samples were classified as RTK I, II, and MES. Full T1ce MRI-based rater consensus was observed in 54 cases, which were retained for further analysis. Epigenetic SVZM classification and SVZ were strongly associated (OR: 15.0, p = 0.003). Thirteen of fourteen differential CpGs were located in the previously described differentially methylated LRBA/MAB21L2 locus. SVZ + tumors were linked to shorter OS (hazard ratio (HR): 3.80, p = 0.02) than SVZM + at earlier time points (time-dependency of SVZM, p < 0.05). Considering the SVZ consensus as the ground truth, SVZM classification yields a sensitivity of 96.6%, specificity of 36.0%, positive predictive value (PPV) of 63.6%, and negative predictive value (NPV) of 90.0%. CONCLUSION: Herein, we validated the specific epigenetic signature in GBM in the vicinity of the SVZ and highlighted the importance of methylation of a part of the LRBA/MAB21L2 gene locus. Whether SVZM can replace MRI-based SVZ assignment as a prognostic and diagnostic tool will require prospective studies of large, homogeneous cohorts.

Growth/differentiation factor 15 controls ependymal and stem cell number in the V-SVZ.

The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs.

The neuronal transcription factor MEIS2 is a calpain-2 protease target.

Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular-subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2.

Single-Nucleus RNA-Seq Characterizes the Cell Types Along the Neuronal Lineage in the Adult Human Subependymal Zone and Reveals Reduced Oligodendrocyte Progenitor Abundance with Age.

The subependymal zone (SEZ), also known as the subventricular zone (SVZ), constitutes a neurogenic niche that persists during postnatal life. In humans, the neurogenic potential of the SEZ declines after the first year of life. However, studies discovering markers of stem and progenitor cells highlight the neurogenic capacity of progenitors in the adult human SEZ, with increased neurogenic activity occurring under pathological conditions. In the present study, the complete cellular niche of the adult human SEZ was characterized by single-nucleus RNA sequencing, and compared between four youth (age 16-22) and four middle-aged adults (age 44-53). We identified 11 cellular clusters including clusters expressing marker genes for neural stem cells (NSCs), neuroblasts, immature neurons, and oligodendrocyte progenitor cells. The relative abundance of NSC and neuroblast clusters did not differ between the two age groups, indicating that the pool of SEZ NSCs does not decline in this age range. The relative abundance of oligodendrocyte progenitors and microglia decreased in middle-age, indicating that the cellular composition of human SEZ is remodeled between youth and adulthood. The expression of genes related to nervous system development was higher across different cell types, including NSCs, in youth as compared with middle-age. These transcriptional changes suggest ongoing central nervous system plasticity in the SEZ in youth, which declined in middle-age.

Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors.

Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/ß-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/ß-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.

Towards validation in clinical routine: a comparative analysis of visual MTA ratings versus the automated ratio between inferior lateral ventricle and hippocampal volumes in Alzheimer's disease diagnosis.

PURPOSE: To assess the performance of the inferior lateral ventricle (ILV) to hippocampal (Hip) volume ratio on brain MRI, for Alzheimer's disease (AD) diagnostics, comparing it to individual automated ILV and hippocampal volumes, and visual medial temporal lobe atrophy (MTA) consensus ratings. METHODS: One-hundred-twelve subjects (mean age ± SD, 66.85 ± 13.64 years) with varying degrees of cognitive decline underwent MRI using a Philips Ingenia 3T. The MTA scale by Scheltens, rated on coronal 3D T1-weighted images, was determined by three experienced radiologists, blinded to diagnosis and sex. Automated volumetry was computed by icobrain dm (v. 5.10) for total, left, right hippocampal, and ILV volumes. The ILV/Hip ratio, defined as the percentage ratio between ILV and hippocampal volumes, was calculated and compared against a normative reference population (n = 1903). Inter-rater agreement, association, classification accuracy, and clinical interpretability on patient level were reported. RESULTS: Visual MTA scores showed excellent inter-rater agreement. Ordinal logistic regression and correlation analyses demonstrated robust associations between automated brain segmentations and visual MTA ratings, with the ILV/Hip ratio consistently outperforming individual hippocampal and ILV volumes. Pairwise classification accuracy showed good performance without statistically significant differences between the ILV/Hip ratio and visual MTA across disease stages, indicating potential interchangeability. Comparison to the normative population and clinical interpretability assessments showed commensurability in classifying MTA "severity" between visual MTA and ILV/Hip ratio measurements. CONCLUSION: The ILV/Hip ratio shows the highest correlation to visual MTA, in comparison to automated individual ILV and hippocampal volumes, offering standardized measures for diagnostic support in different stages of cognitive decline.

Septostomy and Monroplasty in Isolated Lateral Ventricle After Removal of a Third Ventricle Colloid Cyst: 2-Dimensional Operative Video.

Isolated unilateral hydrocephalus (IUH) is a condition caused by unilateral obstruction of the foramen of Monro.1 Etiopathogenic causes include tumors, congenital lesions, infective ventriculitis, intraventricular haemorrhage, and iatrogenic causes such as the presence of contralateral shunts.2,3 Neuroendoscopic management is considered the "gold-standard" treatment in IUH.4 Even if endoscopic septostomy and foraminoplasty in IUH are well-known procedures,5,6 IUH after an interhemispheric transcallosal transchoroidal approach for removal of a III ventricle colloid cyst is a complication barely described in literature. Video 1 describes this rare complication and the neuroendoscopic treatment adopted, including the operative room setup, patient's positioning, instrumentation needed, and a series of intraoperative tips for the performance of septostomy and Monroplasty via a single, precoronal burr hole. The scalp entry point and endoscope trajectory, homolateral to the dilated ventricle, were planned on the neuronavigation system. The avascular septal zone away from the septal veins and body of the fornix was reached, and the ostomy was performed. At the end of the procedure, Monroplasty was performed, too. The procedure was effective in solving the hydrocephalus and patient's clinical picture. No surgical complications occurred. Imaging demonstrated an evident and progressive reduction of enlarged lateral ventricle. In authors' opinion, the single burr-hole approach, ipsilateral to the enlarged ventricle, provides an optimal identification the intraventricular anatomy and allows Monroplasty to be performed, if deemed feasible during surgery. The patient consented to the procedure. The participants and any identifiable individuals consented to publication of their images.

An easy and cost-effective method for the isolation and culturing of neural stem/progenitor cells from the subventricular (SVZ) and dentate gyrus (DG) of adult mouse brain.

BACKGROUND: Isolation of adult Neural Stem/Progenitor Cells (NSPCs) from their neurogenic niches, is a prerequisite for studies involving culturing of NSPCs as neurospheres or attached monolayers in vitro. The currently available protocols involve the use of multiple animals and expensive reagents to establish the NSPCs culture. NEW METHOD: This unit describes a method to isolate and culture NSPCs from the two neurogenic niches in the mouse brain, the Subventricular Zone (SVZ) and Dentate gyrus (DG)/subgranular zone (SGZ), in an easy and cost-effective manner. RESULTS: NSPCs from SVZ and DG regions of adult mouse brains were isolated and cultured up to passage 15 without losing their stem/progenitor characteristics. These NSPCs could be differentiated into neurons, astrocytes, and oligodendrocytes, revealing its trilineage potential. COMPARISON WITH EXISTING METHODS: This protocol eliminates the need for multiple animals as well as the use of many expensive reagents mentioned in previous protocols, adding to the cost-effectiveness of experiments. In addition, we have effectively reduced the number of steps involved in isolation and propagation, thereby minimizing the chances of contamination. CONCLUSION: Our simplified protocol for the isolation and culturing of adult NSPCs from the SVZ and DG demonstrates a cost-effective and efficient alternative to existing methods, reducing the need for sacrificing many animals and the usage of expensive reagents. This method permits the long-term maintenance of NSPCs' stem/progenitor characteristics and their effective differentiation into the major types of cells in the brain, making it a valuable resource for researchers in the field. BASIC PROTOCOL: Isolation and Culturing of Neural Stem/Progenitor cells from the Sub ventricular Zone and the Dentate Gyrus of the adult mouse brain. SUPPORT PROTOCOL 1: Cryopreservation, and revival of frozen NSPCs. SUPPORT PROTOCOL 2: Preparation of adherent monolayer cultures of neural stem/progenitor cells for the differentiation into multiple lineages SUPPORT PROTOCOL 3: Differentiation of NSPCs to neuronal and glial lineages SUPPORT PROTOCOL 4: Characterization of differentiated cells by immunocytochemistry.

Therapeutic hypothermia modulates the neurogenic response of the newborn piglet subventricular zone after hypoxia-ischemia.

BACKGROUND: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. To investigate the neurogenic response to hypoxia-ischemia (HI) followed by normothermia (38.5 °C) or three different hypothermic temperatures (35, 33.5, or 30 °C) in the subventricular zone (SVZ) of the neonatal piglet. METHODS: Following transient cerebral HI and resuscitation, 28 newborn piglets were randomized to: normothermia or whole-body cooling to 35 °C, 33.5 °C, or 30 °C during 2-26 h (all n = 7). At 48 h, piglets were euthanized and SVZ obtained to evaluate its cellularity, pattern of cell death, radial glia length, doublecortin (DCX, neuroblasts) expression, and Ki67 (cell proliferation) and Ki67/Sox2 (neural stem/progenitor dividing) cell counts. RESULTS: Normothermic piglets showed lower total (Ki67+) and neural stem/progenitor dividing (Ki67+Sox2+) cell counts when compared to hypothermic groups. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and DCX immunohistochemistry. Cooling to 30 °C, however, revealed decreased cellularity in the lateral SVZ and shorter radial glia processes when compared with 33.5 °C. CONCLUSIONS: In a neonatal piglet model, hypothermia to 33.5 °C modulates the neurogenic response of the SVZ after HI, highlighting the potential beneficial effect of hypothermia to 33.5 °C on endogenous neurogenesis and the detrimental effect of overcooling beyond this threshold. IMPACT: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. Hypothermia may modulate neurogenesis in the subventricular zone (SVZ) of the neonatal hypoxic-ischemic piglet. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and doublecortin immunohistochemistry; cooling to 30 °C, however, revealed decreased cellularity and shorter radial glia processes. In a neonatal piglet model, therapeutic hypothermia (33.5 °C) modulates the neurogenic response of the SVZ after hypoxia-ischemia, highlighting also the detrimental effect of overcooling beyond this threshold.

Calculation of cerebral hemispheres volume values (grey matter, white matter and lateral ventricle) of sheep and goat: A stereological study.

Stereology is a discipline that allows us to obtain quantitative information about the geometric structure of three-dimensional objects. In this study, the volume of grey matter (GM), white matter (WM), and lateral ventricle (LV) of the cerebral hemispheres (CH) in sheep and goats were calculated. For this purpose, six healthy male sheep and goat brains (1-2 years old) without any anomaly were used. Brains were fixed with 10% formaldehyde in the skull. The skull was opened using standard anatomical dissection methods, and the brains were carefully removed. Brain weight and volume were measured (using Archimedes' principle) after the meninges were removed. The cerebral hemispheres were separated from the other parts of the brain by a section made in front of the rostral colliculus. In the same way, the weight and volume of the cerebral hemispheres were measured. Afterward, the cerebral hemispheres were blocked with agar, and transversal cross sections (from rostral to caudal) with an average thickness of 3.42 mm were taken from the cerebral hemispheres. Grey matter was stained with Berlin blue macroscopic staining method. The stained cross sections were scanned at 600 dpi resolution, and a point counting grid was placed on the images with the ImageJ software. Cavalieri's principle calculated the surface area and volume measurements of the grey matter, white matter, and lateral ventricle. GM, WM, and LV volumes in sheep and goat cerebral hemispheres were calculated as 54.94, 21.48 and 3.06 mL in sheep, 57.46, 24.13 and 3.12 mL in goats, respectively. The percentages of these structures in the total hemisphere volume were 71.83%, 28.17% and 4.00% in sheep, 70.42%, 29.58% and 3.82% in goats, respectively. Asymmetry was not observed in cerebral hemispheres in both species. A difference was found in the WM, LV and LV: CH ratios in the right/left comparison of the goat (p < 0.05). In comparing sheep and goats, a significant difference was observed in WM right, WM left, WM total, CH left and CH total (p < 0.05). In conclusion, the cerebral hemispheres' grey matter and white matter ratio are frequently used to diagnose neurodegenerative diseases. In recent years, the increase in neurodegenerative disease models in farm animals has been enormous. It is thought that these values obtained from healthy animals in the current study will be important for such experimental studies in the future.

[Chordoid gliomas of the third ventricle]. / Opyt lecheniya khordoidnykh gliom III zheludochka.

BACKGROUND: Chordoid glioma is a rare slow-growing tumor of the central nervous system. Available world experience includes no more than 200 cases (lesion of the third ventricle in absolute majority of cases). Recognition and treatment of chordoid glioma are currently difficult problems due to small incidence of this disease. OBJECTIVE: To describe clinical manifestations and surgical treatment of chordoid glioma of the third ventricle considering literature data and own experience. MATERIAL AND METHODS: There were 12 patients (6 men and 6 women) with chordoid glioma between 2004 and 2023 (10 patients with lesion of the third ventricle, 1 - lateral ventricle, 1 - pineal region). Only patients with tumors of the third ventricle were analyzed. RESULTS: Total and subtotal resection was performed in 1 and 3 cases, respectively. Five patients underwent partial resection, 1 patient underwent biopsy. The follow-up data were available in 7 out of 10 patients (mean 25 months). Radiotherapy was performed in 4 patients (continued tumor growth in 2 cases). One patient died. CONCLUSION: Chordoid glioma is a benign tumor predominantly localized in the third ventricle. Preoperative MRI and CT in some cases make it possible to suspect chordoid glioma and differentiate this tumor from craniopharyngioma, meningioma and pituitary adenoma by such signs as isointense signal in T1WI, hyper- or isointense signal in T2WI, homogeneous contrast enhancement and edema of basal ganglia in T2 FLAIR images. The only effective treatment for chordoid glioma is surgery. Total resection is often impossible or extremely dangerous due to location of tumor, large size and invasion of the third ventricle. Postoperative mental disorders and diabetes insipidus, including severe hypernatremia, are common that requires mandatory monitoring of water and electrolyte balance.

High-Grade Gliomas from Subventricular Zone: Proteomic Drivers of Aggressiveness Using Fluorescence-Guided Multiple Sampling.

High-grade gliomas (HGGs) are among the most aggressive brain tumors and are characterized by dismally low median survival time. Of the many factors influencing the survival of patients with HGGs, proximity to the subventricular zone (SVZ) is one of the key influencers. In this context, 5-amino levulinic acid fluorescence-guided multiple sampling (FGMS) offers the prospect of understanding patient-to-patient molecular heterogeneity driving the aggressiveness of these tumors. Using high-resolution liquid chromatography-mass spectrometry (MS)/MS proteomics for HGGs from seven patients (four SVZ associated and three SVZ nonassociated), this study aimed to uncover the mechanisms driving the aggressiveness in SVZ-associated (SVZ+) HGGs. Differential proteomics analysis revealed significant dysregulation of 11 proteins, of which 9 proteins were upregulated and 2 were downregulated in SVZ+ HGGs compared to SVZ-non-associated (SVZ-) HGGs. The gene set enrichment analysis (GSEA) of the proteomics dataset revealed enrichment of MYC targets V1 and V2, G2M checkpoints, and E2F targets in SVZ+ HGGs. With GSEA, we also compared the pathways enriched in glioma stem cell subpopulations and observed a similar expression trend for most pathways in our data. In conclusion, this study reveals new and emerging insights on pathways that may potentially contribute to greater aggressiveness in SVZ+ HGGs. Future studies using FGMS in larger cohorts are recommended to help uncover the proteomics and molecular basis of aggressiveness and stemness in HGGs.

Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone.

Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1ß signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ.

Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers.

Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identified molecular markers of pregnancy-associated interneurons and showed that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient yet behaviorally relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity.