Human testis organoids - a novel stem cell model for reproductive disorders

Summary This project involves optimising the differentiation of human testicular cells from pluripotent stem cells, and growing these to organoid formation. These organoids will then be used to test the importance of new candidate pathogenic gene variants found in DSD patients.

Project Details

Often the first question asked when a child is born is "is it a boy or a girl". Unfortunately, a definitive answer cannot be  given to the parents of a child born with severe ambiguous genitalia. These cases occur with a frequency of 1 in 4500  births and are part of a large spectrum of disorders known as Disorders/Differences of Sex Development (DSD), which  are caused by mutations in the genes that regulate how the testis or ovaries develop and function. Yet, less than 50% of  patients with DSD currently receive a clinical genetic diagnosis. This is due to a very poor understanding of the genes  that can cause DSDs. We use genomic technologies such as Whole Exome Sequencing to find novel candidate genes that  may cause DSDs. We currently test the importance of these gene in the developing gonads (testis or ovaries) using  animal models such as mice. However, mouse gonadal development is not always a good model for human gonadal  development and disease. Consequently, we are developing stem cell technology to grow human testicular cells in a  dish. This project involves optimising the differentiation of human testicular cells from pluripotent stem cells, and  growing these to organoid formation. These organoids will then be used to test the importance of new candidate  pathogenic gene variants found in DSD patients. This project will be conducted in collaboration with Professor Melissa  Little, who has successfully grown human kidney organoids, and used these to model kidney disease. It will suit someone  who has an interest in working with cutting edge stem cell technology to study human disorders.