Discovery of a Novel Regulatory Protein Offers a Novel Tool for Engineering of Stem Cell

These are Bioengineers from the University of California San Diego who have identified a protein that controls the switch of embryonic stem cells from the least introduced naïve state to the more finely developed primed state. Such a discovery sheds light on the stem cell development at a molecular level.

“Such a discovery provides a fine – tuning knob for the stem cell engineering toolkit,” says Sheng Zhang, a bioengineering lecturer at the UC San Diego Jacobs School of Engineering and the study’s senior author.

“A number of conventionally identified regulatory proteins can be considered as rough tuning knobs that lead to greater changes in cellular behaviour. We required both tools to accurately set stem cells into the desired cellular state so that they can carry out the functions that we desire.”

The scientists discovered that the protein, known as SMARCAD1, interacts with a particular sort of histone modification, known as histone circulation, to prevent the spontaneous switch from the naïve to the primed pluripotent state. By suppressing SMARCAD1 from interacting with the H3R26Cit, scientists were able to induce this switch.

They also identified that the stem cells with suppressed SMARCAD1 expression remained pluripotent. “This study offers an approach to fine tune the stem cells between two cellular states corresponding to two early developmental stages,” says Jia Lu, a bioinformatics Ph.D. student in Zhong’s research team who co-authored this study.

Zhong and his group first employed protein arrays composed of hundreds of histone peptides harbouring different post transcriptional modifications, and identified that SMARCAD1 particularly interacts with the H3R26Cit modification. They then employed a technology called as ChIP-seq to assay genome – extensive distributions of SMARCAD1 binding as well as distinct sorts of histone modifications, and found that SMARCAD1 particularly binds to H3R26Cit modified histones in the entire genome.

Scientists also executed studies in which they suppressed the expression of SMARCAD1 and a distinguished set of studies in which they suppressed a more general sort of H3R26Cit called as H3Cit.

In both the studies, they observed cellular alterations consistent with the switch from the naïve to the primed stem cell state, offering more evidence of SMARCAD1’s regulatory role in the stem cell development. Moving forward, the group is investigating whether SMARCAD1 also plays a role in regulating the nature of cancer cells.