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Artificial induction of circadian rhythm by combining exogenous BMAL1 expression and polycomb repressive complex 2 inhibition in human induced pluripotent stem cells
Creating a daily biological clock in human stem cells by adding BMAL1 and blocking a gene-silencing complex
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Abstract
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).
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