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Series GSE45469 Query DataSets for GSE45469
Status Public on Jan 01, 2016
Title Induced Pluripotency of Human Prostatic Epithelial Cells
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen, a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified key pathways and regulators of prostatic differentiation including Wnt5a, BPM7, PTEN, and NKx3.1 using E-PZ-iPS-lke cells. Our results suggest that iPS-like cells can be derived from prostatic epithelial cells. These cells are pluripotent and capable of prostatic differentiation, and therefore provide a novel model for investigating epigenetic changes involved in prostate cell lineage specification.
Overall design Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium HumanMethylation450K Beadchip v1.2
Web link
Contributor(s) Zhao H, Peehl DM
Citation(s) 23717621
Submission date Mar 25, 2013
Last update date Mar 22, 2019
Contact name Hongjuan Zhao
Organization name Stanford
Department Urology
Lab Donna Peehl
Street address 300 Pasteur Dr
City Stanford
State/province CA
ZIP/Postal code 95014
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (10)
GSM1105107 E-PZ-1-iPS-like-4 in control medium AR day 1
GSM1105108 E-PZ-1-iPS-like-4 in induction medium AR day 1
GSM1105109 E-PZ-1-iPS-like-4 in control medium AR day 3
BioProject PRJNA194105

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE45469_RAW.tar 183.1 Mb (http)(custom) TAR
GSE45469_signals.txt.gz 40.1 Mb (ftp)(http) TXT
Processed data included within Sample table

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