BioProject

With the increasing common of reduced serum testosterone (T), or hypogonadism, in the male population, there is an urgent require for the approach of obtaining T-producing cells, which could be used to treat hypogonadism based on transplantation and reestablishment of T-producing cell lineage in the body. More...

With the increasing common of reduced serum testosterone (T), or hypogonadism, in the male population, there is an urgent require for the approach of obtaining T-producing cells, which could be used to treat hypogonadism based on transplantation and reestablishment of T-producing cell lineage in the body. In human, T is mainly synthesized by the Leydig cells (LCs) that have been proposed to derive from mesenchymal cells of mesonephric origin. Although mesenchymal cells have been successfully induced into LCs, the limited source and possible trauma to donors hinders their wide applications in clinic therapies. Alternatively, human induced pluripotent stem cells (hiPSCs) that are highly expandable in cell culture and have the potential to differentiate into all somatic cell types become the emerging source of autologous cell therapies. In this study, we have successfully induced the differentiation of hiPSCs through mesoderm and early mesenchymal progenitors (EMPs) into either human Leydig cell-like cells (hLLCs) or human adrenal cell-like cells (hALCs) under different chemically defined culture systems. Factors that are critical for the normal development of LCs were added to both culture systems. hLLCs are expressed all steroidogenic genes and proteins that are important for T biosynthesis and are specific for LCs, synthesize T rather than cortisol (F), secret steroid hormones in response to db-cAMP and 22(R)-hydroxycholesterol, and display ultrastructural features resembling LCs. Differentially, hALCs synthesize F rather than T, and secret much less of steroid hormones than hLLCs. Thereafter, we performed microarray analyses to profile the whole gene expression pattern of hiPSCs and thier derivatives hLLCs and hALCs. Overall design: The hiPSC line GM25256*B was induced to differentiate into human Leydig cell-like cells (hLLCs) and human adrenal cell-like cells (hALCs), respectively. Transcriptome profiling was performed using transcriptome microarrays. Each cell types including three replicates were collected and profiled. Less...