Developing mouse inhibitory neuron single-cell transcriptomes reveal distinct modes of cell-type diversification
TL;DR
A computational pipeline is developed to enrich and integrate rare cell types across datasets and applied to somatostatin-expressing (SST+) inhibitory neurons, revealing that the developing cortex builds inhibitory diversity through three routes—early commitment, gradual diversification and selective elimination.
Abstract
The cerebral cortex depends on a diverse repertoire of inhibitory neurons, yet how this diversity emerges during development remains unclear. Rare inhibitory subtypes are often underrepresented in single-cell RNA-sequencing datasets, limiting resolution of their developmental trajectories. Here we developed a computational pipeline to enrich and integrate rare cell types across datasets and applied it to somatostatin-expressing (SST+) inhibitory neurons, the most diverse inhibitory class in cortex. We generated Dev-SST-v1 and Dev-SST-v2, transcriptomic reference maps comprising more than 55,000 mouse SST+ neurons. These maps identify three major SST+ inhibitory neuron groups—Martinotti cells (MCs), non-Martinotti cells (nMCs) and long-range projecting (LRP) neurons—each defined by a distinct developmental strategy. MCs commit early, whereas nMCs diversify progressively. LRPs follow a contracting trajectory, with one transient subtype eliminated by programmed cell death. Together, these findings establish three distinct modes of SST+ inhibitory neuron diversification, including a previously unrecognized contracting mode. Researchers discover a transient inhibitory cell type, and reveal that the developing cortex builds inhibitory diversity through three routes—early commitment, gradual diversification and selective elimination.