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

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Final rept. 7 May 2012-6 May 2014

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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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  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology

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