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Neuroendocrinology of the lung revealed by single cell RNA sequencing

Christin S. Kuo, Spyros Darmanis, Alex Diaz de Arce, Yin Liu, Nicole Almanzar, Timothy T.H. Wu, Stephen R. Quake, Mark A. Krasnow
doi: https://doi.org/10.1101/2022.03.08.483399
Christin S. Kuo
1Department of Pediatrics, Stanford University School of Medicine, Stanford, California, 94305, USA
2Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA
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Spyros Darmanis
3Department of Bioengineering, Stanford University, Stanford, California, 94305, USA
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Alex Diaz de Arce
2Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA
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Yin Liu
2Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA
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Nicole Almanzar
1Department of Pediatrics, Stanford University School of Medicine, Stanford, California, 94305, USA
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Timothy T.H. Wu
2Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA
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Stephen R. Quake
3Department of Bioengineering, Stanford University, Stanford, California, 94305, USA
4Chan-Zuckerburg Biohub, San Francisco, California, USA
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Mark A. Krasnow
2Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA
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  • For correspondence: krasnow@stanford.edu
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ABSTRACT

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 10, 2022.
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Neuroendocrinology of the lung revealed by single cell RNA sequencing
Christin S. Kuo, Spyros Darmanis, Alex Diaz de Arce, Yin Liu, Nicole Almanzar, Timothy T.H. Wu, Stephen R. Quake, Mark A. Krasnow
bioRxiv 2022.03.08.483399; doi: https://doi.org/10.1101/2022.03.08.483399
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Neuroendocrinology of the lung revealed by single cell RNA sequencing
Christin S. Kuo, Spyros Darmanis, Alex Diaz de Arce, Yin Liu, Nicole Almanzar, Timothy T.H. Wu, Stephen R. Quake, Mark A. Krasnow
bioRxiv 2022.03.08.483399; doi: https://doi.org/10.1101/2022.03.08.483399

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