Doxycycline Masks the Genuine Effect of the Doxycycline-Inducible Transgene by Promoting Dopaminergic Neuron Differentiation from Human Pluripotent Stem Cells.

Doxycycline (DOX), an antibacterial drug, has been widely used in the inducible gene expression system. However, its effect was largely ignored when studying functions of the inducible transgene. By using a DOX-inducible Tet-ON system, we identified that DOX alone dramatically promoted dopaminergic (DA) neuron differentiation from human pluripotent stem cells (hPSCs), whereas the studied gene had no significant effects after considering the confounding factor DOX. These findings suggest that the effect of DOX should be taken into consideration when it is used in the inducible system especially during DA neuron differentiation from hPSCs. Meanwhile, it also suggests that DOX can be used as an efficient and inexpensive molecule to increase DA neuron differentiation efficacy from hPSCs for cell therapy.