Journal article
Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells
iScience, Vol.23(5), pp.101083-101083
05/22/2020
DOI: 10.1016/j.isci.2020.101083
PMCID: PMC7205764
PMID: 32380423
Abstract
Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (<1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs), which express core PNEC markers, including ROBO receptors, and secrete major neuropeptides, recapitulating known functions of primary PNECs. Furthermore, we demonstrate that differentiation efficiency is increased in the presence of an air-liquid interface and inhibition of Notch signaling. Single-cell RNA sequencing (scRNA-seq) revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In addition, pseudotime analysis of scRNA-seq results suggests a basal cell origin of human iPNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases.
Details
- Title: Subtitle
- Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells
- Creators
- Pooja Hor - Hastings CenterVasu Punj - University of Southern CaliforniaBen A Calvert - Hastings CenterAlessandra Castaldi - Hastings CenterAlyssa J. Miller - University of MichiganGianni Carraro - Cedars-Sinai Medical CenterBarry R. Stripp - Cedars-Sinai Medical CenterSteven L. Brody - Washington University in St. LouisJason R. Spence - University of MichiganJustin K. Ichida - University of Southern CaliforniaAmy L. Ryan (Firth) - University of Southern CaliforniaZea Borok - University of Southern California
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.23(5), pp.101083-101083
- DOI
- 10.1016/j.isci.2020.101083
- PMID
- 32380423
- PMCID
- PMC7205764
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- Elsevier
- Number of pages
- 34
- Grant note
- USC Broad Innovation Award Hastings Foundation U01HL122642; 1U01HL122638 / National Heart, Lung, and Blood Institute (NHLBI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R35HL135747; R00NS077435; R01NS097850 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA New York Stem Cell Foundation
- Language
- English
- Date published
- 05/22/2020
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284457902771
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