{Reference Type}: Journal Article
{Title}: A Chemical Biology Study of Human Pluripotent Stem Cells Unveils HSPA8 as a Key Regulator of Pluripotency.
{Author}: Geng Y;Zhao Y;Schuster LC;Feng B;Lynn DA;Austin KM;Stoklosa JD;Morrison JD;
{Journal}: Stem Cell Reports
{Volume}: 5
{Issue}: 6
{Year}: Dec 2015 8
{Factor}: 7.294
{DOI}: 10.1016/j.stemcr.2015.09.023
{Abstract}: Chemical biology methods such as high-throughput screening (HTS) and affinity-based target identification can be used to probe biological systems on a biomacromolecule level, providing valuable insights into the molecular mechanisms of those systems. Here, by establishing a human embryonal carcinoma cell-based HTS platform, we screened 171,077 small molecules for regulators of pluripotency and identified a small molecule, Displurigen, that potently disrupts hESC pluripotency by targeting heat shock 70-kDa protein 8 (HSPA8), the constitutively expressed member of the 70-kDa heat shock protein family, as elucidated using affinity-based target identification techniques and confirmed by loss-of-function and gain-of-function assays. We demonstrated that HSPA8 maintains pluripotency by binding to the master pluripotency regulator OCT4 and facilitating its DNA-binding activity.