Stem cell-based therapies and cellular reprogramming holds immense potential for regenerative medicine. Therefore, significant effort has been invested to develop methods for effectively controlling the differentiation of stem cells into specific line-ages. One promising approach for enhancing gene expression and inducing stem cell differentiation involves epigenetic modification. Epigenetic modification refers to changes in gene activity and expression by modifying chromatin structure rather than altering the DNA sequence.
Recently, under the guidance of Prof. KiBum Lee at Rutgers University, a team of researchers led by Sahishnu Patel developed a novel epigenetic modulator called CTB. CTB is a small molecule that functions by altering the chromatin architecture to modulate gene expression.
In their recently published paper, they report a new CTB derivative with increased solubility and demonstrate CTB’s functionality by conjugating it on the recently established NanoScript platform to enhance gene expression and induce stem cell differentiation. NanoScript is a nanoparticle-based artificial transcription factor that emulates the structure and function of transcription factor proteins, which was previously demonstrated NanoScript to effectively regulate endogenous gene expression.
They hypothesized that by modifying NanoScript with CTB, they can more closely replicate the structure of transcription factor proteins, demonstrate enhancement of CTB functionality, and enhance gene expression. To this end, they first conjugated CTB onto NanoScript which initiated a time-dependent increase in histone acetyltransferace (HAT) activity. Second, because CTB is known to trigger the pathway involved in regulating Sox9, a master regulator of chondrogeneic differentiation, they modified a Sox9-specific NanoScript with CTB enhanced chondrogeneic gene activity and differentiation.
In doing so, they enhanced the NanoScript platform with an epigenetic modulator (CTB derivative), and because NanoScript is a tunable and robust platform, it has potential for various gene-regulating applications such as stem cell differentiation.
- Patel, S.; Pongkulapa, T.; Yin, P. T.; Pandian, G. N.; Rathnam, C.; Bando, T.; Vaijayanthi, T.; Sugiyama, H.; Lee, K.-B. Integrating Epigenetic Modulators into NanoScript for Enhanced Chondrogenesis of Stem Cells. Journal of the American Chemical Society 2015, 137, 4598-4601.
Prof. KiBum Lee
Year of Research Highlight: 2015