eLife (Dec 2022)

Neuroendocrinology of the lung revealed by single-cell RNA sequencing

  • Christin S Kuo,
  • Spyros Darmanis,
  • Alex Diaz de Arce,
  • Yin Liu,
  • Nicole Almanzar,
  • Timothy Ting-Hsuan Wu,
  • Stephen R Quake,
  • Mark A Krasnow

DOI
https://doi.org/10.7554/eLife.78216
Journal volume & issue
Vol. 11

Abstract

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Pulmonary neuroendocrine cells (PNECs) are sensory epithelial cells that transmit airway status to the brain via sensory neurons and locally via calcitonin gene-related peptide (CGRP) and γ- aminobutyric acid (GABA). Several other neuropeptides and neurotransmitters have been detected in various species, but the number, targets, functions, and conservation of PNEC signals are largely unknown. We used scRNAseq to profile hundreds of the rare mouse and human PNECs. This revealed over 40 PNEC neuropeptide and peptide hormone genes, most cells expressing unique combinations of 5–18 genes. Peptides are packaged in separate vesicles, their release presumably regulated by the distinct, multimodal combinations of sensors we show are expressed by each PNEC. Expression of the peptide receptors predicts an array of local cell targets, and we show the new PNEC signal angiotensin directly activates one subtype of innervating sensory neuron. Many signals lack lung targets so may have endocrine activity like those of PNEC-derived carcinoid tumors. PNECs are an extraordinarily rich and diverse signaling hub rivaling the enteroendocrine system.

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