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<p>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<sup>+</sup>) 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<sup>+</sup> neurons. These maps identify three major SST<sup>+</sup> 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<sup>+</sup> inhibitory neuron diversification, including a previously unrecognized contracting mode.</p>

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Developing mouse inhibitory neuron single-cell transcriptomes reveal distinct modes of cell-type diversification

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Minhui Liu,
  • Facundo Ferrero Restelli,
  • Elia Micoli,
  • Giulia Barbiera,
  • Rani Moors,
  • Evelien Nouboers,
  • Malou Reverendo,
  • Jessica Xinyun Du,
  • Hannah Bertels,
  • Dimitris Konstantopoulos,
  • Keimpe Wierda,
  • Aya Takeoka,
  • Giordano Lippi,
  • Lynette Lim

摘要

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.