title: Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells.
abstract: BACKGROUND
  Induced pluripotent stem cells (iPSCs) hold tremendous potential, both as a biological tool to uncover the pathophysiology of disease by creating relevant human cell models and as a source of cells for cell-based therapeutic applications. Studying the reprogramming process will also provide significant insight into tissue development.
  
  
  OBJECTIVE
  We sought to characterize the derivation of iPSC lines from nasal epithelial cells (NECs) isolated from nasal mucosa samples of children, a highly relevant and easily accessible tissue for pediatric populations.
  
  
  METHODS
  We performed detailed comparative analysis on the transcriptomes and methylomes of NECs, iPSCs derived from NECs (NEC-iPSCs), and embryonic stem cells (ESCs).
  
  
  RESULTS
  NEC-iPSCs express pluripotent cell markers, can differentiate into all 3 germ layers in vivo and in vitro, and have a transcriptome and methylome remarkably similar to those of ESCs. However, residual DNA methylation marks exist, which are differentially methylated between NEC-iPSCs and ESCs. A subset of these methylation markers related to epithelium development and asthma and specific to NEC-iPSCs persisted after several passages in vitro, suggesting the retention of an epigenetic memory of their tissue of origin. Our analysis also identified novel candidate genes with dynamic gene expression and DNA methylation changes during reprogramming, which are indicative of possible roles in airway epithelium development.
  
  
  CONCLUSIONS
  NECs are an excellent tissue source to generate iPSCs in pediatric asthmatic patients, and detailed characterization of the resulting iPSC lines would help us better understand the reprogramming process and retention of epigenetic memory.
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio. Electronic address: Hong.Ji@cchmc.org.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Human Genetics, Kim Sook Za Children's Hospital Medical Center Research Foundation, Cheongju, South Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Oh
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Mayhew
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ulm
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Hari K
authors.initials: HK
authors.lastname: Somineni
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Mark
authors.initials: M
authors.lastname: Ericksen
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: James M
authors.initials: JM
authors.lastname: Wells
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Gurjit K
authors.initials: GK
authors.lastname: Khurana Hershey
mesh_terms: D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D057890:Epigenomics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts; D052816:Foreskin / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000166:cytology*
keywords: DNA methylation; Induced pluripotent stem cells; asthma; epigenetic memory; gene expression; nasal epithelial cells