The compound StemRegenin 1 (SR1) is a selective, cell-permeable, small molecule that promotes the self-renewal of human hematopoietic stem cells in culture. SR1 is an antagonist of the aryl hydrocarbon receptor. SR1 is the first small molecule that promotes robust expansion/self-renewal of human CD34 peripheral blood and cord blood hematopoietic stem cells (HSCs). The culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. SR1 can be potentially used for ex vivo expansion of normal HSCs or leukemic stem/progenitor cells