@article{353b06d68d7240628d21a38796039ed0,
title = "Efficient Generation and Transcriptomic Profiling of Human iPSC-Derived Pulmonary Neuroendocrine Cells",
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.",
keywords = "Cell Biology, Stem Cells Research, Transcriptomics",
author = "Pooja Hor and Vasu Punj and Calvert, {Ben A.} and Alessandra Castaldi and Miller, {Alyssa J.} and Gianni Carraro and Stripp, {Barry R.} and Brody, {Steven L.} and Spence, {Jason R.} and Ichida, {Justin K.} and {Ryan (Firth)}, {Amy L.} and Zea Borok",
note = "Funding Information: We acknowledge the use of the services at the USC Optical Imaging Facility, Genomics Core in the Department of Biomedical Sciences at the Cedars-Sinai Medical Center, and the LungMAP Consortium. This work was supported by NIH grants R35HL135747 , R00NS077435 , and R01NS097850 ; the New York Stem Cell Foundation ; the USC Broad Innovation Award; and the Hastings Foundation . J.K.I. is a New York Stem Cell Foundation-Robertson Investigator. Z.B. is Ralph Edgington Chair in Medicine and Hastings Professor of Medicine. The LungMAP Consortium ( U01HL122642 ) and the LungMAP Data Coordinating Center ( 1U01HL122638 ) are funded by the National Heart, Lung, and Blood Institute (NHLBI). Funding Information: We acknowledge the use of the services at the USC Optical Imaging Facility, Genomics Core in the Department of Biomedical Sciences at the Cedars-Sinai Medical Center, and the LungMAP Consortium. This work was supported by NIH grants R35HL135747, R00NS077435, and R01NS097850; the New York Stem Cell Foundation; the USC Broad Innovation Award; and the Hastings Foundation. J.K.I. is a New York Stem Cell Foundation-Robertson Investigator. Z.B. is Ralph Edgington Chair in Medicine and Hastings Professor of Medicine. The LungMAP Consortium (U01HL122642) and the LungMAP Data Coordinating Center (1U01HL122638) are funded by the National Heart, Lung, and Blood Institute (NHLBI). Conceptualization, P.H. A.L.R. and Z.B.; Methodology, P.H. J.K.I. A.L.R. and Z.B.; Investigation, P.H. V.P. S.L.B, J.R.S. B.A.C. B.R.S. A.C. A.J.M. and J.R.S.; Writing ? Original Draft, P.H. A.L.R.; Writing ? Review & Editing, P.H. A.L.R. J.K.I. and Z.B.; Funding Acquisition, J.K.I. and Z.B.; Resources, J.K.I. A.L.R. and Z.B.; Supervision, J.K.I. A.L.R. and Z.B. J.K.I. is a co-founder of AcuraStem Incorporated. J.K.I. declares that he is bound by confidentiality agreements that prevent him from disclosing details of his financial interests in this work. All data needed to evaluate the conclusions in the article are present in the article paper and/or the Supplemental Information. Additional data related to this article may be requested from the authors. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = may,
day = "22",
doi = "10.1016/j.isci.2020.101083",
language = "English",
volume = "23",
journal = "iScience",
issn = "2589-0042",
number = "5",
}