Stem cell differentiation into steroidogenic cell lineages by NR5A family.

Transformants of mesenchymal stem cells (MSCs) stably expressing steroidogenic factor-1 (SF-1) undergo differentiation into steroidogenic cell-lineages by stimulation with cyclic-adenosine mono-phosphate (cAMP). Another member of NR5A nuclear orphan receptors, Liver-specific receptor homologue-1 (LRH-1), was also able to differentiate MSCs. On the other hand, we found that embryonic stem (ES) cells were hardly induced to differentiate into steroidogenic cell-lineage by the similar treatment. In this study, we developed a novel method to differentiate ES cells into steroidogenic cells. We introduced SF-1 into mouse ES cells at ROSA26 locus under regulation of Tetracycline-off (Tet-off) in order to express SF-1 in the cells at desired period. When SF-1 was induced to express after the ES cells had been differentiated into mesenchymal cell-lineage, steroid hormones were produced from the SF-1 expressing cells. This provides a safer method for supplying sufficient amount of differentiated cells toward future regenerative medicine.