Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

Abstract

We set out to establish conditions for differentiation of human neonatal foreskin skin fibroblast-derived iPSCs into prostate epithelium-like cells and identify differences in gene expression between prostate epithelial cells derived from iPSCs of Caucasian and African-American foreskin fibroblasts. We identified and optimized culture conditions that promote prostate epithelial cell-like differentiation of human iPS clone, IMAR90-4. Our data show that a feeder layer of urogenital mesenchymal (UGSM) cells from neonatal mouse of either gender in combination with neonatal human dermal fibroblasts induced a striking morphological changes that resembles epithelial differentiation with formation of lumen-like structures. We showed requirement of the extracellular matrix of components that promote epithelial-type differentiation. Immunofluorescence and biochemical analyses showed expression of androgen receptor and markers of epithelial differentiation. Analyses of pluripotency marker expression by RT-PCR showed that while human dermal fibroblasts have higher constitutive expression of Nanog, Oct4 and Sox2 compared to IMP90 cells. Our studies showed that black fibroblasts have higher constitutive expression of pluripotency markers than cells from white skin. These data form the basis for studies on the differences in reprogramming of skin fibroblasts and their differentiation into prostate epithelial cells and susceptibility to transformation.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2014
Accession Number
ADA609443

Entities

People

  • Vijayasaradhi Setaluri

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • African Americans
  • Androgen Receptors
  • Androgens
  • Cancer
  • Caucasians
  • Cells
  • Culture Techniques
  • Epithelial Cells
  • Epithelium
  • Gene Expression
  • Genitalia
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Stem Cells
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).
  • Toxicology/Environmental Toxicology

Technology Areas

  • Biotechnology