Sensitivity of baboon and human progenitors to growth factors may be responsible for the ability of baboon progenitors to synthesize high HbF levels relative to human progenitors in liquid cultures. Interestingly, our results show that effects of various stromal cell lines on globin gene ICG-001 Wnt/beta-catenin inhibitor expression in the co-culture system did not correlate with the developmental stage of origin of the stromal lines. Specifically, the yolk sac and fetal liver-derived cell lines decreased c-globin expression while high levels of cglobin expression were observed in co-cultures with an adult BMderived stromal cell line. Further analysis of differential gene expression patterns between these lines could identify candidate factors responsible for these effects. While the stromal micro-environment is capable of inhibiting the increased c-globin expression observed in cultured adult bone marrow derived erythroid progenitors, it is incapable of repressing c-globin expression in cord blood-derived progenitors or decitabine-treated adult bone marrow-derived progenitors, suggesting that permissive epigenetic signals such as DNA hypomethylation of the c-globin promoter may be dominant to repressive stromal cell factors. Our results support the model stating that developmental switching is controlled by a cell-intrinsic developmental clock based on transplantation experiments perfomed in sheep. These transplantation experiments were performed in a single species, in contrast to transplantation experiments of human cord blood cells into NOD/SCID mice where a switch from predominately fetal to adult globin gene expression was observed. Cord blood contains a mix of progenitors programmed to express either a fetal or adult globin program and it is possible that species differences in growth factors crossreactivities and growth factor requirements of these different progenitors could have allowed preferential expansion and differentiation of progenitors expressing the adult globin program in the NOD/SCID mouse. In adult progenitors may foster the development of additional therapeutic strategies that interfere with this switch to enhance HbF expression for the treatment of hemoglobinopathies. Cardiac hypertrophy is an early hallmark and important risk factor for the development of heart failure. Hypertrophy of cardiomyocytes occurs in response to pathological stimuli such as hypertension, aortic valve stenosis, myocardial infarction or genetic mutations in sarcomeric proteins and is regarded as a maladaptive process, since left ventricular hypertrophy often progresses to heart failure. Cardiac hypertrophy is accompanied by reprogramming of cardiac gene expression and the activation of ‘fetal’ cardiac genes encoding proteins involved in contraction, calcium handling and metabolism. Specific transcription factors such as MEF2, GATA4, NFAT, SRF and myocardin have been identified that activate this fetal gene program. Besides these transcriptional factors that promote cardiac hypertrophy, it has also become increasingly evident that the heart possesses a variety of endogenous feedback mechanisms to counterbalance this growth response. We and others recently identified the transcriptional regulator KLF15 as an inhibitor of cardiac gene expression and hypertrophy. Mouse studies showed that somatic loss of KLF15 results in increased susceptibility to pressure overload-induced LVH and heart failure.