Adult stem cells necessitate a transcriptional state that sustains multipotency and self-renewal for lifetime. Hematopoietic Stem Cells (HSC) are the source of all blood cells and lead both biological study and clinical utilization of stem cells – by saving thousands every year with bone-marrow transplant. However, understanding how HSC sustain stem-cell state is still limited. During my PostDoc I have generated and analyzed extensive microarrays expression datasets, identifying numerous candidate-regulators for HSCs. One of the top-hits, Hlf, also showed robust in vitro induction of HSC-like immunephenotype and functional activity. Now, focusing on Hlf aims to elucidate the molecular networks of transcriptome regulation in primitive primary hematopoietic cells. With the generation of a new reporter/conditional knockout mouse the endogenous role of Hlf will be further revealed. Taken together, this proposal continues my previous research, and going to shed new light on HSC regulation. Implications of such findings are relevant to lymphoma, and to development of novel ways to increase utilization of HSCs.