During the reporting period, we have made significant progress toward the following research aims: (1) Established two screening assay conditions that allowed us to carry out high throughput screens of small molecules for enhancing conversion of conventional human ESCs to the earlier developmental naive state like murine embryonic stem cells. A couple of hit compounds were identified from the screen, and validated. (2). Established and characterized naive state human pluripotent cell lines converted from HUES7, HUES10 and classic H1. Human pluripotent stem cells in such naive state exhibit similar cellular behaviors, e.g., cell survival, proliferation, and responses to various signaling pathway modulations as mES cells. (3) Identified a new fundamental mechanism in such reprogramming/conversion process.