Blood cells are turned over rapidly and we carry a relatively modest number of stem cells to regenerate them. One of the key properties to understand is how these cells stably maintain the undifferentiated state. To study this, we have taken the approach of determining how these cells are programmed. We have lineage traced the cells in Xenopus and zebrafish embryos to determine their history and the niches that they occupy. We have then searched these niches for the signals that programme the cells. We have also begun to identify the nuclear responses to these signals that lead to the establishment of a stable networks of transcription factors that specify cell fate. We have taken a similar approach to the myocardium, and more recently have begun to compare normal development with regeneration. We are attempting to identify the cells, signals and transcriptional networks involved in this process, an understanding of which could inform regenerative strategies in the human heart.