PT  - JOURNAL ARTICLE
AU  - Kuo, Christin S.
AU  - Darmanis, Spyros
AU  - Diaz de Arce, Alex
AU  - Liu, Yin
AU  - Almanzar, Nicole
AU  - Wu, Timothy T.H.
AU  - Quake, Stephen R.
AU  - Krasnow, Mark A.
TI  - Neuroendocrinology of the lung revealed by single cell RNA sequencing
AID  - 10.1101/2022.03.08.483399
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.08.483399
4099  - http://biorxiv.org/content/early/2022/03/10/2022.03.08.483399.short
4100  - http://biorxiv.org/content/early/2022/03/10/2022.03.08.483399.full
AB  - Pulmonary neuroendocrine cells (PNECs) are sensory epithelial cells that transmit airway status to the brain via sensory neurons and locally via CGRP and 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 >40 PNEC neuropeptide and peptide hormone genes, most cells expressing unique combinations of 5-18 genes. Peptides are packaged in separate vesicles, release presumably regulated by the distinct, multimodal combinations of sensors expressed by each PNEC. Expression of cognate receptors predicts an array of local targets, and we show the new PNEC signal angiotensin directly activates innervating sensory neurons. 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.Competing Interest StatementThe authors have declared no competing interest.