Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium.

McCauley KB, Alysandratos KD, Jacob A, Hawkins F, Caballero IS, Vedaie M, Yang W, Slovik KJ, Morley M, Carraro G, Kook S, Guttentag SH, Stripp BR, Morrisey EE, Kotton DN
Stem Cell Reports. 2018 10 (5): 1579-1595

PMID: 29657097 · PMCID: PMC5995784 · DOI:10.1016/j.stemcr.2018.03.013

Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the characterization of these cells. Here, we engineer mouse and human PSC lines carrying airway secretory lineage reporters that facilitate the tracking, purification, and profiling of this lung subtype. Through bulk and single-cell-based global transcriptomic profiling, we find PSC-derived airway secretory cells are susceptible to phenotypic plasticity exemplified by the tendency to co-express both a proximal airway secretory program as well as an alveolar type 2 cell program, which can be minimized by inhibiting endogenous Wnt signaling. Our results provide global profiles of engineered lung cell fates, a guide for improving their directed differentiation, and a human model of the developing airway.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (21)

Animals Cell Differentiation Cell Line Cell Lineage Cell Plasticity Epithelium Gene Expression Profiling Genes, Reporter Humans Induced Pluripotent Stem Cells Kinetics Lung Mice Secretoglobins Sequence Analysis, RNA Single-Cell Analysis Solubility Spheroids, Cellular Time Factors Transcriptome Wnt Signaling Pathway

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