Transplanted cells do not always integrate properly into host circuitry and can cause suboptimal graft function or undesired outcomes.To determine if the function of human stem cell-derived neurons can be regulated,we engineered human embry-onic stem cells (hESCs) by CRISPR to express the excitatory or inhibitory from of DREADDs (designer receptor exclusively activated by designer drug).In culture,the membrane and action potentials of the DREADD-expressing midbrain dopamine (mDA) neurons differentiated from the transgenic hESCs were precisely regulated by a designer drug clozapine-N-oxide (CNO).Four months following transplantation into the striatum of Parkinsons disease mice,the human mDA neurons innervated the striatum extensively.Electrophysiological analysis indicated that the human mDA neurons form functional connections with and regulate host striatal GABA neurons via the D1 receptors.Behavioral analyses (rotation,cylinder,ro-tarod) indicated that the transplanted animals recovered from motor deficits.Importantly,the mouse motor recovery was reversed or enhanced after inhibiting or activating the graft function by CNO,respectively.The ability to control the graft function enables refining the therapeutic outcomes remotely,thus raising the prospect of stem cell therapy.