Molecular Signatures and Lineage Diversification of Neurogenic and Gliogenic Radial Glia in the Gyrencephalic Ferret Cortex
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PROVIDER: PRJNA1303047 | ENA |
REPOSITORIES: ENA
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Project description:Human exceptional cognition stems from evolutionarily derived cortical adaptations that drive expansive neurogenesis. Deciphering these mechanisms is crucial for understanding mammalian cortical evolution. In this study, we employ the ferret model to comprehensively map molecular profiles and lineage dynamics of cortical radial glia (RGs). By applying scRNA-Seq to ferret and human cortices, we identify conserved regulatory programs underlying cortical neurogenesis and gliogenesis in mammals. Through integrated scRNA-Seq, BrdU pulse-chase labeling, and immunohistochemical approaches, we demonstrate that, similar to their human counterparts, ferret cortical outer radial glia (oRGs), exhibit enhanced ERK and PKA signaling. ERK and PKA act in a mutually reinforcing manner to boost oRG self-renewal and neurogenesis, while inhibiting gliogenesis and prolonging the neurogenic period. Furthermore, we identify regional specialization within cortical gliogenic RGs: YAP/TAZ activation drives ventricular zone truncated radial glia (tRGs) toward ependymal fate in medial cortex, whereas SHH signaling instructs lateral cortical tRGs to generate tripotential intermediate progenitor cells, which serve as a shared source of astrocytes, oligodendrocytes, and olfactory bulb interneurons. Our data support a model in which mammalian cortical neurogenesis, gliogenesis, and evolutionary expansion are co-regulated through an integrated signaling network involving ERK, PKA, YAP/TAZ, and SHH. These findings provide key insights into the molecular and cellular mechanisms driving cortical development and evolution.
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Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of ; these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia. Experiment Overall Design: Comparison of radial glial subtypes
2008-06-18 | E-GEOD-8034 | biostudies-arrayexpress
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: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.
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Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia.
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Project description:Single cell RNA-seq study of induced pluripotent stem cell derived neural stem cells. Analysis of gene expression over cell clusters identified inherent presence of neurogenic progenitors and gliogenic progenitors in established neural stem cells. This study aids to explain heterogeneity of neural stem cell identity and resolves gene expression enrichment in subpopulations of diverse progenitors. Processed and quality controlled data sets used for generating figure 4 in published article. Single cell raw data files for experiments were not made available.
2019-10-24 | E-MTAB-8363 | biostudies-arrayexpress
Project description:Single cell RNA-seq study of induced pluripotent stem cell derived neural stem cells. Analysis of gene expression over cell clusters identified inherent presence of neurogenic progenitors and gliogenic progenitors in established neural stem cells. This study aids to explain heterogeneity of neural stem cell identity and resolves gene expression enrichment in subpopulations of diverse progenitors. Processed and quality controlled data sets used for generating figure 2 in published article. Single cell raw data files for experiments are not available for public download.
2019-10-24 | E-MTAB-8379 | biostudies-arrayexpress
Project description:Single cell RNA-seq study of induced pluripotent stem cell derived neural stem cells. Analysis of gene expression over cell clusters identified inherent presence of neurogenic progenitors and gliogenic progenitors in established nerual stem cells. This study aids to explain heterogeneity of neural stem cell identity and resolves gene expression enrichment in subpopulations of diverse progenitors. Processed and quality controlled data sets used for generating figure 3 in published article. Single cell raw data files for experiments are not available for public download.
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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.
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