Kristine M. Abo,1,2 Julio Sainz de Aja,3,4,5 Jonathan Lindstrom-Vautrin,1 Konstantinos-Dionysios Alysandratos,1,2 Alexsia Richards,6 Carolina Garcia-de-Alba,3,4,5 Jessie Huang,1,2 Olivia T. Hix,1,2 Rhiannon B. Werder,1,2 Esther Bullitt,7 Anne Hinds,2 Isaac Falconer,8 Carlos Villacorta-Martin,1 Rudolf Jaenisch,6,9 Carla F. Kim,3,4,5 Darrell N. Kotton,1,2 and Andrew A. Wilson1,2
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts, USA.
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
3Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children’s Hospital, Boston, Massachusetts, USA.
4Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
5Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
6Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
7Department of Physiology & Biophysics, Boston University, Boston, Massachusetts, USA.
8Boston University School of Medicine, Boston, Massachusetts, USA.
9Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
This study comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. They find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. Then they leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor.