Vision-dependent specification of cell types and function in the developing cortex
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PROVIDER: PRJNA788967 | ENA |
REPOSITORIES: ENA
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Project description:The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA-sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ~200 genes, including regulators of cell adhesion and synapse formation. One of these, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell type-specific gene expression programs.
2021-12-27 | GSE190940 | GEO
Project description:Molecular specification of cell types underlying central and peripheral vision in primates
| PRJNA485982 | ENA
Project description:The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. One of these genes, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell-type-specific gene expression programs.
| S-EPMC8813006 | biostudies-literature
Project description:During development, the human brain orchestrates the generation of hundreds of diverse cell types, and recent transcriptomic atlases of the developing human cortex provide new opportunities to identify novel regulators of cell fate specification. We have conducted an integrated meta-analysis of seven recently published single-cell transcriptomic profiles of the developing human cortex, generating a meta-atlas of 225 meta-modules. By tracking the activity of these meta-modules throughout development and comparing this to datasets from the adult human as well as the developing and adult mouse, we identified modules with potential roles in the transition from neurogenesis to gliogenesis and neuronal subtype maturation. The cell type and developmental state at which these modules exist was validated in primary samples from the developing human brain. Of particular interest, we identified and validated a module associated with both developing human deep layer neurons and human adult deep layer neuronal subtypes expressing the terminal differentiation marker FEZF2. Though FEZF2 is neither a member of nor co-expressed with our deep layer-associated gene module, almost half of module genes are putative FEZF2 targets, including TSHZ3, a transcription factor associated with neurodevelopmental disorders such as autism. Knockdown experiments in human cortical organoid models confirm that both FEZF2 and TSHZ3 are necessary for deep layer neuron specification. Importantly, we observe that subtle manipulations of these transcription factors result in slight changes in module activity, but together yield strong differences in cell fate. Our analyses therefore reveal a gene network that required to generate deep layer neuronal subtypes, demonstrating the ability of our meta-atlas to engender further mechanistic analyses of cortical fate specification. We anticipate this resource being useful for the study of co-expression programs across diverse biological questions related to the developing neocortex.
2023-09-12 | GSE242779 | GEO
Project description:During development, the human brain orchestrates the generation of hundreds of diverse cell types, and recent transcriptomic atlases of the developing human cortex provide new opportunities to identify novel regulators of cell fate specification. We have conducted an integrated meta-analysis of seven recently published single-cell transcriptomic profiles of the developing human cortex, generating a meta-atlas of 225 meta-modules. By tracking the activity of these meta-modules throughout development and comparing this to datasets from the adult human as well as the developing and adult mouse, we identified modules with potential roles in the transition from neurogenesis to gliogenesis and neuronal subtype maturation. The cell type and developmental state at which these modules exist was validated in primary samples from the developing human brain. Of particular interest, we identified and validated a module associated with both developing human deep layer neurons and human adult deep layer neuronal subtypes expressing the terminal differentiation marker FEZF2. Though FEZF2 is neither a member of nor co-expressed with our deep layer-associated gene module, almost half of module genes are putative FEZF2 targets, including TSHZ3, a transcription factor associated with neurodevelopmental disorders such as autism. Knockdown experiments in human cortical organoid models confirm that both FEZF2 and TSHZ3 are necessary for deep layer neuron specification. Importantly, we observe that subtle manipulations of these transcription factors result in slight changes in module activity, but together yield strong differences in cell fate. Our analyses therefore reveal a gene network that required to generate deep layer neuronal subtypes, demonstrating the ability of our meta-atlas to engender further mechanistic analyses of cortical fate specification. We anticipate this resource being useful for the study of co-expression programs across diverse biological questions related to the developing neocortex.
2024-12-06 | GSE278573 | GEO
Project description:Molecular specification of cell types underlying central and peripheral vision in primates (macaque fovea single cell RNA-seq)
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Project description:Molecular specification of cell types underlying central and peripheral vision in primates (macaque peripheral single cell RNA-seq)
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Project description:A Meta-Atlas of the Developing Human Cortex Identifies Modules Driving Cell Subtype Specification
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Project description:Among mammals, only primates including human possess a small central retinal region called the fovea, which mediates high acuity vision. As other mammals lack a fovea, molecular bases of its specialized function and dysfunction in retinal diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we identified and molecularly characterized >60 major cell types in each region. A few cell types are unique to each region, and there are also substantial differences in proportions and gene expression between corresponding types in the two areas, some of which can be related to functional differences. Comparison of macaque and mouse retinal taxonomies reveals both similarities and differences between species. Many molecular features of macaque retinal cell types are conserved in two other primates, marmosets and humans, and key human retinal disease-associated genes are expressed in specific macaque cell types
2019-02-06 | GSE118852 | GEO
Project description:Among mammals, only primates including human possess a small central retinal region called the fovea, which mediates high acuity vision. As other mammals lack a fovea, molecular bases of its specialized function and dysfunction in retinal diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we identified and molecularly characterized >60 major cell types in each region. A few cell types are unique to each region, and there are also substantial differences in proportions and gene expression between corresponding types in the two areas, some of which can be related to functional differences. Comparison of macaque and mouse retinal taxonomies reveals both similarities and differences between species. Many molecular features of macaque retinal cell types are conserved in two other primates, marmosets and humans, and key human retinal disease-associated genes are expressed in specific macaque cell types
2019-02-06 | GSE118546 | GEO