A functional genomics approach to investigate the differentiation of iPSCs into lung epithelium at air‐liquid interface

• DOI: 10.1111/jcmm.15568
• Publication Date: 2020-07-21T14:06:20Z
• Authors: Jenny L. Kerschner; Alekh Paranjapye; Shiyi Yin; Dannielle L. Skander; Gurkan Bebek; Shih‐Hsing Leir; Ann Harris
• Keywords: CTCF

Abstract The availability of robust protocols to differentiate induced pluripotent stem cells (iPSCs) into many human cell lineages has transformed research the origins disease. efficacy differentiating iPSCs specific cellular models is influenced by factors including both intrinsic and extrinsic features. Among most challenging generation bronchial epithelium at air‐liquid interface (HBE‐ALI), which gold standard for studies respiratory diseases cystic fibrosis. Here, we perform open chromatin mapping ATAC‐seq transcriptomics RNA‐seq in parallel, define functional genomics key stages iPSC HBE‐ALI differentiation. Within peaks, overrepresented motifs include architectural protein CTCF all stages, while FOXA pioneer GATA factor families are seen more often early those regulating airway epithelial functions, such as EHF, limited later stages. data illustrate dynamic pathways during differentiation, also marked divergence different lines ALI Moreover, a comparison iPSC‐derived lung donor‐derived cultures reveals substantial differences between these models.