Significance We established human embryonic stem (hES) cell-inducible lines to express specific transcription factors [GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1)] to improve medium spiny neuron (MSN) differentiation and to study human striatal development in vitro. We also used a nonintegrating system, by utilizing modified mRNAs to transiently overexpress Gsx2 and Ebf1 in a different hES cell line. These data can help to improve the differentiation protocols that aim to produce high-quality cell preparation suitable for cell transplantation in animal models of Huntington’s disease. Finally, we show that hES-derived striatal progenitors can be transplanted in the striatum of animal models and can differentiate and integrate into the host, extending fibers over a long distance (including the substantia nigra, a striatal target).