neural progenitor cell

BACKGROUND: Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma. METHODS: We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas ( n  = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings...

The plant homeodomain finger protein Phf8 is a histone demethylase implicated by mutation in mice and humans in neural crest defects and neurodevelopmental disturbances. Considering its widespread expression in cell types of the central nervous system, we set out to determine the role of Phf8 in oligodendroglial cells to clarify whether oligodendroglial defects are a possible contributing factor to Phf8-dependent neurodevelopmental disorders. Using loss- and gain-of-function approaches in oligodendroglial cell lines and primary cell cultures, we show that Phf8 promotes the proliferation of rodent oligodendrocyte progenitor cells and impairs their differentiation to oligodendrocytes...

Intracellular calcium plays a pivotal role in central nervous system (CNS) development by regulating various processes such as cell proliferation, migration, differentiation, and maturation. However, understanding the involvement of calcium (Ca2+ ) in these processes during CNS development is challenging due to the dynamic nature of this cation and the evolving cell populations during development. While Ca2+ transient patterns have been observed in specific cell processes and molecules responsible for Ca2+ homeostasis have been identified in excitable and non-excitable cells, further research into Ca2+ dynamics and the underlying mechanisms in neural stem cells (NSCs) is required...

Idiopathic intellectual disability ( IID ) encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology. However, in idiopathic ID, the effect of miRNAs is poorly understood. The aim of this study was to determine the miRNAs regulating the expression of mRNAs that may be involved in development of IID ...

Studying the properties of neural stem progenitor cells (NSPCs) in a fish model will provide new information about the organization of neurogenic niches containing embryonic and adult neural stem cells, reflecting their development, origin cell lines and proliferative dynamics. Currently, the molecular signatures of these populations in homeostasis and repair in the vertebrate forebrain are being intensively studied. Outside the telencephalon, the regenerative plasticity of NSPCs and their biological significance have not yet been practically studied...

The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood-brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells...

Glioblastoma is one of the most common and aggressive brain tumors and has seen few improvements in patient outcomes. Inter-tumor heterogeneity between tumors of different patients as well as intra-tumor heterogeneity of cells within the same tumor challenge the development of effective drugs. MiRNAs play an essential role throughout the developing brain and regulate many key genes involved in oncogenesis, yet their role in driving many of the processes underlying tumor heterogeneity remains unclear. In this study, we highlight miRNAs from the Dlk1-Dio3 and miR-224/452 clusters which may be expressed cell autonomously and have expression that is associated with cell state genes in glioblastoma, most prominently in neural progenitor-like and mesenchymal-like states respectively...

Embryonic neurogenesis can be defined as a period of prenatal development during which divisions of neural stem and progenitor cells give rise to neurons. In the central nervous system of most mammals, including humans, the majority of neocortical neurogenesis occurs before birth. It is a highly spatiotemporally organized process whose perturbations lead to cortical malformations and dysfunctions underlying neurological and psychiatric pathologies, and in which oxygen availability plays a critical role. In case of deprived oxygen conditions, known as hypoxia, the hypoxia-inducible factor (HIF) signaling pathway is activated, resulting in the selective expression of a group of genes that regulate homeostatic adaptations, including cell differentiation and survival, metabolism and angiogenesis...

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested structures...

BACKGROUND: MLC901 is a phytopharmaceutical comprising significant compounds that can induce microenvironments conducive to the proliferation and specialization of neural cell progenitors. This study investigates the impact of administering MLC901, reducing the expression of NG2 and caspase-3 and increasing IL-10 levels, as well as histopathological and motor function, after severe spinal cord injury (SCI) in the chronic phase. METHODS: The study employed a randomized post-test-only control group design conducted between February and April 2023 at the Integrated Biomedical Laboratory...

Neural progenitor cells within the cerebral cortex undergo a characteristic switch between symmetric self-renewing cell divisions early in development and asymmetric neurogenic divisions later. Yet, the mechanisms controlling this transition remain unclear. Previous work has shown that early but not late neural progenitor cells (NPCs) endogenously express the autism-linked transcription factor Foxp1, and both loss and gain of Foxp1 function can alter NPC activity and fate choices. Here, we show that premature loss of Foxp1 upregulates transcriptional programs regulating angiogenesis, glycolysis, and cellular responses to hypoxia...

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics...

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells...

Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ...

Continuous immunosuppression has been widely used in xenografts into non-human primate brains. However, how immune responses change after transplantation in host brains under continuous immunosuppressive administration and whether immunosuppression can be withdrawn to mitigate side effects remain unclear. Human induced neural stem/progenitor cells (iNPCs) have shown long-term survival and efficient neuronal differentiation in primate brains. Here, we evaluate the immune responses in primate brains triggered by human grafts...

In a developing embryo, formation of tissues and organs is remarkably precise in both time and space. Through cell-cell interactions, neighboring progenitors coordinate their activities, sequentially generating distinct types of cells. At present, we only have limited knowledge, rather than a systematic understanding, of the underlying logic and mechanisms responsible for cell fate transitions. The formation of the dorsal aspect of the spinal cord is an outstanding model to tackle these dynamics, as it first generates the peripheral nervous system and is later responsible for transmitting sensory information from the periphery to the brain and for coordinating local reflexes...

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types...

Alzheimer's disease accounts for 60-70% of dementia cases. Current treatments are inadequate and there is a need to develop new approaches to drug discovery. Recently, in cancer, morphological profiling has been used in combination with high-throughput screening of small-molecule libraries in human cells in vitro . To test feasibility of this approach for Alzheimer's disease, we developed a cell morphology-based drug screen centred on the risk gene, SORL1 (which encodes the protein SORLA). Increased Alzheimer's disease risk has been repeatedly linked to variants in SORL1 , particularly those conferring loss or decreased expression of SORLA, and lower SORL1 levels are observed in post-mortem brain samples from individuals with Alzheimer's disease...

This study evaluates the sustained antidepressant-like effects and neurogenic potential of a 3-day intranasal co-administration regimen of galanin receptor 2 (GALR2) agonist M1145 and neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31, Pro34]NPY in the ventral hippocampus of adult rats, with outcomes analyzed 3 weeks post-treatment. Utilizing the forced swimming test (FST), we found that this co-administration significantly enhances antidepressant-like behaviors, an effect neutralized by the GALR2 antagonist M871, highlighting the synergistic potential of these neuropeptides in modulating mood-related behaviors...

Although genome wide association studies (GWAS) have identified loci for sleep-related traits, they do not directly uncover the underlying causal variants and corresponding effector genes. The majority of such variants reside in non-coding regions and are therefore presumed to impact cis-regulatory elements. Our previously reported 'variant-to-gene mapping' effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in both Drosophila and zebrafish, implicated PIG-Q as a functionally relevant gene at the insomnia 'WDR90' GWAS locus...