Single-cell transcriptome profiling of radial glia cells in zebrafish adult telencephalon in response to traumatic brain injury
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE209705 | GEO | 2024/07/22
REPOSITORIES: GEO
Similar Datasets
Project description:Traumatic brain injuries (TBIs) represent a large global disease burden and can result in several short- and long-term deficits. Treatment for TBIs are limited, however stem cell therapies involving either transplantation of exogenous stem cells or stimulation of endogenous stem cells have been proposed. These approaches possess issues with survival and differentiation of stem/progenitor cells, which highlights the need to elucidate mechanisms necessary for complete regeneration. Zebrafish exhibit a robust neuronal regenerative capacity following damage in various parts of the central nervous system. In this study, we use a modified blunt-force TBI (bfTBI) model, the most common type of TBI seen in the human population, to damage the adult zebrafish telencephalon and examine cellular and molecular consequences. This model induces a variety of TBI-related phenotypes across different injury severities, which mimic the pathologies observed following bfTBI in humans. Additionally, we show that after bfTBI, cells in the zebrafish telencephalon, including radial glia (RGC), non-glial neural progenitors (NPs), and neuroblasts, proliferate and differentiate into various neural cell types. We performed a snRNA-Seq analysis of the damaged and regenerating telencephalon, which revealed heterogeneity among the progenitor cells. Further, the snRNA-Seq demonstrated that quiescent radial glia became activated upon injury and yielded neural progenitor cells. To functionally assess how the regenerative process is regulated, we knocked down the expression of PdgfrB and demonstrated that it played a role in maintaining RGC quiescence. Collectively, this study provides a foundation for future studies of neuronal regeneration in the adult zebrafish telencephalon following a bfTBI.
2024-10-04 | GSE278446 | GEO
Project description:Single-cell transcriptome profiling of radial glia cells in zebrafish adult telencephalon in response to traumatic brain injury
| PRJNA862132 | ENA
Project description:Zebrafish display widespread and pronounced adult neurogenesis, which is fundamental for their regeneration capability after central nervous system injury. However, the cellular identity and the biological properties of adult newborn neurons are elusive for most brain areas. Here, we used short-term lineage tracing of radial glia progeny to prospectively isolate newborn neurons from the her4.1+ radial glia lineage in the homeostatic adult forebrain. Transcriptome analysis of radial glia, newborn neurons and mature neurons using single cell sequencing identified distinct transcriptional profiles including novel markers for each population. Specifically, we detected 2 separate newborn neuron types, which showed diversity of cell fate commitment and location. Further analyses showed homology of these cell types to neurogenic cells in the mammalian brain, identified neurogenic commitment in proliferating radial glia and indicated that glutamatergic projection neurons fate are generated in the adult zebrafish telecephalon. Thus, we prospectively isolated adult newborn neurons from the adult zebrafish forebrain, identified markers for newborn and mature neurons in the adult brain, revealed intrinsic heterogeneity among adult newborn neurons and their homology to mammalian adult neurogenic cell types.
2019-11-27 | GSE137525 | GEO
Project description:The African turquoise killifish combines a short lifespan with age-dependent loss of neuroregenerative capacity, making it a well-suited model for studying brain repair mechanisms in the context of aging. To investigate the extent of cellular diversity that shapes neuro- and gliogenesis, we performed single cell sequencing of the adult telencephalon. Our analysis identifies seventeen cell types including neuronal cells, and progenitors of glial and non-glial nature. Further subclustering unveils four radial glia (RG) types, one atypical non-glial progenitor (NGP) and two intermediate subtypes. Validation of our data in situ reveals a distinct spatial setting for defined RG subtypes, reflecting the distribution of morphologically and physiologically distinct populations. Lineage inference analysis suggests neuroepithelial-like radial glia and NGP to be the start point and intercessor of neural development, respectively. Neuronal sub-clustering uncovers immature and mature excitatory or inhibitory sub-clusters. This complete catalogue of killifish telencephalon cell types is accessible via an online tool, providing a resource to understand neurogenesis in healthy brains and upon injury or disease.
2024-09-03 | GSE213154 | GEO
Project description:<p>The human neocortex is created from diverse intermixed progenitors in the prenatal germinal zones. These progenitors have been difficult to characterize since progenitors - particularly radial glia (RG) - are rare, and are defined by a combination of intracellular markers, position and morphology. To circumvent these problems we developed a method called FRISCR (Fixed and Recovered Intact Single Cell RNA) for transcriptome profiling of individual fixed, stained and sorted cells. We developed and validated FRISCR on human embryonic stem cells. We then profiled primary human RG (96 - 132 days post conception) that constitute only 1% of the mid-gestation cortex. These RG could be classified into ventricular zone-enriched RG (vRG) that express ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that express HOPX. Our study identifies the first markers and molecular profiles of vRG and oRG cells, and provides an essential step for understanding molecular networks driving the lineage of human neocortical progenitors.</p> <p><i>Reprinted from Thomsen et. al. Nature Methods (2015), with permission from Nature Publishing.</i></p> <p>Human embryonic stem cell data may be obtained through NCBI's GEO database, using accession number <a href="http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71858">GSE71858</a>. Raw data from one human sample that was not consented to be released to dbGaP may be obtained directly from the authors of Thomsen et. al., 2015.</p>
| phs001016 | dbGaP
Project description:Neural cell type diversity arises from both spatial and temporal patterning of neural stem cells. Although spatial patterning mechanisms have been extensively studied, temporal patterning mechanisms remain relatively unexplored. In this study, we addressed generation of diverse neural cell types through lineage progression of mouse cortical radial glia. The time series scRNA-seq and snATAC-seq of mouse cortical development revealed that radial glia temporally transitioned from neurogenesis to gliogenesis. During gliogenic stages, various cell types were generated simultaneously along multidirectional lineage trajectories. We established comprehensive molecular maps for cortical lineage commitment and cellular diversification. The transcriptome and epigenome of cortical radial glia exhibit temporal dynamics, as revealed by scRNA-seq and snATAC-seq. Lhx2, a transcription factor with temporal dynamic chromatin binding activities, was identified as a key regulator of the neurogenesis-to-gliogenesis transition. It maintains neurogenic competence by establishing the active epigenetic state of its target genes.
2024-09-03 | GSE276209 | GEO
Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.
2022-02-20 | GSE165351 | GEO
Project description:The evolution of nervous systems hinges on cell type diversification and specialization. Neural glia, also called macroglia, make up a large percentage of the total cell numbers in the brain of several species including humans and perform critical functions related to producing, maintaining and assiting neurons. Despite their importance, glial cells have been much less studied than neurons. Here, in order to investigate the heterogeneity of adult radial glial cells in zebrafish and to study the evolution of macroglia and the adult neurogenesis process they support, we generated a single cell RNAseq dataset of the adult zebrafish telencephalon enriched for radial glial cells using a sox2:gfp transgenic line.
2023-02-26 | GSE225863 | GEO
Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.
2022-02-20 | GSE166569 | GEO
Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.
2022-02-20 | GSE165813 | GEO