Transcriptome and proteome characterization of surface ectoderm cells differentiated from human iPSCs

Sci Rep. 2016 Aug 23:6:32007. doi: 10.1038/srep32007.

Abstract

Surface ectoderm (SE) cells give rise to structures including the epidermis and ectodermal associated appendages such as hair, eye, and the mammary gland. In this study, we validate a protocol that utilizes BMP4 and the γ-secretase inhibitor DAPT to induce SE differentiation from human induced pluripotent stem cells (hiPSCs). hiPSC-differentiated SE cells expressed markers suggesting their commitment to the SE lineage. Computational analyses using integrated quantitative transcriptomic and proteomic profiling reveal that TGFβ superfamily signaling pathways are preferentially activated in SE cells compared with hiPSCs. SE differentiation can be enhanced by selectively blocking TGFβ-RI signaling. We also show that SE cells and neural ectoderm cells possess distinct gene expression patterns and signaling networks as indicated by functional Ingenuity Pathway Analysis. Our findings advance current understanding of early human SE cell development and pave the way for modeling of SE-derived tissue development, studying disease pathogenesis, and development of regenerative medicine approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 4 / pharmacology*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Diamines / pharmacology*
  • Ectoderm / cytology*
  • Ectoderm / drug effects
  • Ectoderm / metabolism
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Proteomics / methods*
  • Signal Transduction / drug effects
  • Thiazoles / pharmacology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • 24-diamino-5-phenylthiazole
  • Bone Morphogenetic Protein 4
  • Diamines
  • Thiazoles
  • Transforming Growth Factor beta