Cyclin D1 acts as a barrier to pluripotent reprogramming by promoting neural progenitor fate commitment

•Cyclin D1 is coexpressed with neural progenitor markers during reprogramming.•Subpopulations of reprogramming cells exhibit distinct cell-cycle properties.•Elevated levels of cyclin D1 impair plurioteny maintenance.•Cyclin D1 regulates neural fate commitment via transcriptionally regulating Pax6. A short G1 phase is a characteristic feature of the cell cycle structure of pluripotent cells, and is reestablished during Yamanaka factor-mediated pluripotent reprogramming. How cell cycle control is adjusted to meet the requirements of pluripotent cell fate commitment during reprogramming is less well understood. Elevated levels of cyclin D1 were initially found to impair pluripotency maintenance. The current work further identified Cyclin D1 to be capable of transcriptionally upregulating Pax6, which promoted reprogramming cells to commit to a neural progenitor fate rather than a pluripotent cell fate. These findings explain the importance of reestablishment of G1-phase restriction in pluripotent reprogramming.