VATIS UPDATE Article

Bioengineers at the University of California San Diego, the United States, have discovered a protein that regulates the switch of embryonic stem cells from the least developed “naïve” state to the more developed “primed” state. This discovery sheds light on stem cell development at a molecular level. “This discovery provides a fine-tuning knob for the stem cell engineering toolkit,” said Sheng Zhong, at the UC San Diego.

The researchers discovered that the protein, called SMARCAD1, interacts with a specific type of histone modification, called histone citrullination (H3R26Cit), to prevent the spontaneous switch from the naïve to the primed pluripotent state. By suppressing SMARCAD1 from interacting with H3R26Cit, researchers were able to induce this switch. They also found that the stem cells with suppressed SMARCAD1 expression remained pluripotent.

Researchers first used protein arrays composed of hundreds of histone peptides harboring distinct post-transcriptional modifications, and found that SMARCAD1 specifically interacts with the H3R26Cit modification. They then used a technology called ChIP-seq to assay genome-wide distributions of SMARCAD1 binding as well different kinds of histone modifications, and found that SMARCAD1 specifically binds to H3R26Cit modified histones in the entire genome.