Transcription regulation of hematopoietic stem cell self-renewal and differentiation to T lineages
Hematopoietic stem cells (HSCs) are capable of self-renewal to maintain its own homeostasis and differentiation to all blood cells. We are interested in how these processes are regulated on the transcription level, focusing on two groups of major transcription factors, GABP and TCF-1/LEF-1. GABP (GA binding protein) is an Ets family transcription factor, consisting of DNA binding GABP α subunit and transactivating GABP β subunit. GABP has critical roles in regulating basic cellular functions such as cell cycle progression and mitochondrial respiration. We and others have demonstrated its lineage-specific roles. We are currently investigating how GABP contributes to HSC homeostasis and its differentiation to T lineage cells. TCF-1 (T cell factor-1) and LEF-1 (lymphoid enhancer-binding factor 1) are the effector transcription factors of Wnt signaling pathway, which has versatile roles in development, differentiation, and oncogenesis. In spite of extensive studies, the exact roles of these factors in HSC maintenance, T cell development and activation remains to be elucidated. We are using gene targeting, molecular biology, and bioinformatics approaches to dissect the function of each of these transcription factors and their possible interactions in hematopoiesis.