Single cell transcriptomics reveals developmental hierarchies of the human forebrain

old_uid14367
titleSingle cell transcriptomics reveals developmental hierarchies of the human forebrain
start_date2017/09/22
schedule14h
onlineno
detailsInvited By Colette Dehay and Henry Kennedy
summaryNeurons of the cerebral cortex emerge from radial glia cells of the developing telencephalon. To systematically identify the major sources of molecular variation related to developmental stage of maturation, differentiation and anatomical location within cells of the same type, we used single cell RNA sequencing (scRNA-seq) in human cortex and medial ganglionic eminence (MGE). We describe a molecular signature of radial glia patterning, maturation and subtype identity. By comparing lineages leading to excitatory and inhibitory neurons, we define a molecular signature of differentiation common to the excitatory and inhibitory neurogenesis, with additional gene networks providing lineage-specific differentiation programs. Within cortex, we compared differentiation signatures in the visual and prefrontal areas and showed that a small number of transcriptional differences among radial glia cascade during neuronal differentiation into robust distinctions between transcriptional states of excitatory neurons. Together, single cell transcriptional states support a mixed model of topographical and typological hierarchies governing cell type diversity in the developing telencephalon. Our study provides a framework for studying patterns of continuous gene expression variation during development.
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