Reprogramming of prostate cancer-associated stromal cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35373 | GEO | 2012/01/28
SECONDARY ACCESSION(S): PRJNA152605
REPOSITORIES: GEO
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Project description:CD90+ prostate cancer-associated (CP) stromal cells represent a disease cell type found only in tumor tissue. Genetic reprogramming by induced pluripotent stem (iPS) cell technology might be used to “normal gene expression of diseased cells thereby providing a cure. The resultant iPS cells would no longer express the disease program, and, like stem cells, might respond to normal differentiative signaling. Thus, CP stromal cells, isolated from tumor tissue and cultured in vitro, were transfected with POU5F1/LIN28/NANOG/SOX2 lentiviral vectors. iPS cells were obtained at a frequency of 10^4. Transcriptome analysis showed an almost complete match in gene expression between the iPS cells and human embryonic stem cells. Genes of CP stromal cells were fully inactivated. CP stromal cells were isolated from tissue, cultured and transfected with lentiviral vectors containing NANOG, SOX2, POU5F1, LIN28. The resultant induced pluripotent cells were analyzed by DNA microarrays.
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Project description:Induced pluripotent stem (iPS) cells can be generated from somatic cells by transduction with several transcription factors in both mouse and human. However, direct reprogramming in other species has not been reported. Here, we established an efficient method to generate monkey iPS cells from fibroblasts by retrovirus-mediated introduction of the four monkey transcription factors OCT4 (POU5F1), SOX2, KLF4, and c-MYC. The monkey iPS cells displayed ES-like morphology, expressed ES cell-marker genes, shared similar global gene profiles and methylation status in the OCT4 promoter to those of monkey ES cells, and possessed the ability to differentiate into three germ layers in vitro and in vivo. Our results suggest that the mechanism of direct reprogramming is conserved among species. The efficient generation of monkey iPS cells will allow investigation of the feasibility of therapeutic cloning in primate model with various diseases. Keywords: Induced pluripotent stem, iPS, Rhesus monkey
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