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Publication : Molecular logic of cellular diversification in the mouse cerebral cortex.

First Author  Di Bella DJ Year  2021
Journal  Nature Volume  595
Issue  7868 Pages  554-559
PubMed ID  34163074 Mgi Jnum  J:323958
Mgi Id  MGI:7264829 Doi  10.1038/s41586-021-03670-5
Citation  Di Bella DJ, et al. (2021) Molecular logic of cellular diversification in the mouse cerebral cortex. Nature 595(7868):554-559
abstractText  The mammalian cerebral cortex has an unparalleled diversity of cell types, which are generated during development through a series of temporally orchestrated events that are under tight evolutionary constraint and are critical for proper cortical assembly and function(1,2). However, the molecular logic that governs the establishment and organization of cortical cell types remains unknown, largely due to the large number of cell classes that undergo dynamic cell-state transitions over extended developmental timelines. Here we generate a comprehensive atlas of the developing mouse neocortex, using single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing. We sampled the neocortex every day throughout embryonic corticogenesis and at early postnatal ages, and complemented the sequencing data with a spatial transcriptomics time course. We computationally reconstruct developmental trajectories across the diversity of cortical cell classes, and infer their spatial organization and the gene regulatory programs that accompany their lineage bifurcation decisions and differentiation trajectories. Finally, we demonstrate how this developmental map pinpoints the origin of lineage-specific developmental abnormalities that are linked to aberrant corticogenesis in mutant mice. The data provide a global picture of the regulatory mechanisms that govern cellular diversification in the neocortex.
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