MRC MRes/PhD Studentship - Characterisation of A Human Induced Pluripotent Stem Cell Model Of Prostate Differentiation

Studies of highly prevalent prostate diseases, such as benign prostatic hyperplasia and prostate cancer, are compromised by the lack of clinically relevant models using human prostate tissue. Although primary culture models exist, they are hampered by the small number of cells that can be cultured, viability beyond 2-4 weeks and altered phenotypes. A potential solution is the use of adult cells reprogrammed into embryonic stem cells (ESCs), called induced pluripotent stem cells (iPSCs), which offer a theoretical limitless supply of cells that can be differentiated into prostate cells. Generation of tissue-specific iPSCs is important, as iPSCs show preferential differentiation into the lineages from which they were derived because of methylation imprinting from the parent somatic cell. Our laboratory is the first to generate human prostate iPSCs, using an Oct4-Sox2-Klf4-cMyc polycistronic lentivirus, and we have shown that an early prostate-like phenotype can be regenerated. Of note, iPSCs derived from skin was unable to differentiate into mature prostate cells. These findings confirm prostate iPSC generation, but the full extent of prostate differentiation requires further characterisation.

In this study we will assess if human prostate derived iPSCs can regenerate fully differentiated prostate-like glands in vivo. This will involve the introduction of differentiation and lineage specific fluorescent markers to allow tracing of prostate iPSCs differentiation. Characterisation of this prostate stem cell differentiation model will provide new insights into the mechanisms of prostate disease.