Extending the pluripotency of hematopoietic stem cells (HSC) is of key importance to the application of stem cell therapies in a variety of diseases. Loss of the expression of the cell surface proteins CD34 and CD133 is one marker of HSC differentiation and thus often monitored in assays to test potential compounds that promote HSC expansion. StemRegenin 1 (SR1) is a purine derivative that antagonizes aryl hydrocarbon receptor signaling with an IC50 value of 127 nM in CD34+ cells, which results in sustained expression of CD34. Human embryonic stem cells cultured with SR1 show a 50-fold increase in cells expressing CD34 (EC50 = 120 nM) and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. This effect is quickly reversed with removal of SR1, which leads to rapid cell differentiation.
