Creating a daily biological clock in human stem cells by adding BMAL1 and blocking a gene-silencing complex

Circadian rhythm was induced in human iPSCs by targeting specific molecular mechanisms.

• Human-induced pluripotent stem cells (iPSCs) do not show circadian oscillation of clock genes.
• This lack of rhythmicity may be linked to the repression of clock genes through hypermethylation of histone H3 at lysine 27 (H3K27).
• Low levels of brain and muscle ARNT-like 1 (BMAL1) protein may also contribute to the absence of circadian rhythm in iPSCs.
• Overexpression of BMAL1 in iPSCs led to the induction of a significant circadian rhythm.
• Treatment with GSK126, an inhibitor of a specific methyltransferase, combined with BMAL1 overexpression resulted in rhythmic expression of clock genes such as period 2 (PER2).

Simplified