Chronic nicotine differentially affects murine transcriptome profiling in isolated cortical interneurons and pyramidal neurons
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE89899 | GEO | 2017/06/12
SECONDARY ACCESSION(S): PRJNA354278
REPOSITORIES: GEO
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Project description:The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge through the implementation of different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons, as they represent a relatively small proportion of all cortical cells, migrate tangentially from their embryonic origin to the cerebral cortex, and have a protracted development. Here we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells, the most diverse subclass of inhibitory neurons in the mouse cerebral cortex. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is further refined during early postanal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons. Thus, the diversification of SST+ inhibitory neurons involves a temporal cascade of unique molecular programs driving their divergent developmental trajectories.
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Project description:The goal of this project was to assess how alternative splicing programs are arrayed across neuronal cells types. We systematically mapped ribosome-associated transcript isoforms in genetically-defined neuron types of the mouse forebrain. The endogenous ribosomal protein Rpl22 was conditionally HA-tagged in glutamatergic neurons (using CamK2-cre for most neocortical pyramidal cells and Scnn1a-cre for spiny stellate and star pyramid layer 4 cells), and GABAergic interneurons [with somatostatin-cre (SST), parvalbumin-cre (PV) and vasointestinal peptide-cre (VIP)]. Within the hippocampus, we further targeted Cornu ammonis 1 (CA1) neurons (CamK2-cre), CA3 neurons (Grik4-cre), and SST-positive interneurons (SST-cre). Four replicates were deep sequenced (~100 million reads) using an Illumina platform. We find that neuronal transcript isoform profiles reliably distinguish even closely-related classes of pyramidal cells and inhibitory interneurons in the mouse hippocampus and neocortex, positing transcript diversification by alternative splicing as a central mechanism for the functional specification of neuronal cell types and circuits.
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