Title: Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium.
Authors: McCauley, Katherine B; Alysandratos, Konstantinos-Dionysios; Jacob, Anjali; Hawkins, Finn; Caballero, Ignacio S; Vedaie, Marall; Yang, Wenli; Slovik, Katherine J; Morley, Michael; Carraro, Gianni; Kook, Seunghyi; Guttentag, Susan H; Stripp, Barry R; Morrisey, Edward E; Kotton, Darrell N
Published In Stem Cell Reports, (2018 05 08)
Abstract: 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.
PubMed ID: 29657097
MeSH Terms: Animals; Cell Differentiation/genetics; Cell Line; Cell Lineage; Cell Plasticity; Epithelium/metabolism*; Epithelium/ultrastructure; Gene Expression Profiling*; Genes, Reporter; Humans; Induced Pluripotent Stem Cells/cytology; Induced Pluripotent Stem Cells/metabolism*; Kinetics; Lung/cytology*; Mice; Secretoglobins/metabolism; Sequence Analysis, RNA; Single-Cell Analysis*; Solubility; Spheroids, Cellular/cytology; Spheroids, Cellular/metabolism; Time Factors; Transcriptome/genetics; Wnt Signaling Pathway