Department of Pathology
The University of Chicago
Donnelley Biological Sciences Learning Center (BSLC)
Jules F. Knapp Medical Research Center (JFK)
924 E. 57th Street, Room R-318
Chicago, IL 60637
The development of mature hematopoietic cells requires the coordinated activity of many transcription factors that regulate differentiation, survival, and proliferation. My lab is interested in understanding how these processes are controlled during commitment of multipotent cells to the lymphoid lineages. We have focused on the basic helix-loop-helix transcription factors encoded by the E2A gene and their antagonists, the Id proteins. E2A proteins are required for B lymphocyte development whereas their antagonist, Id2, is required for Natural Killer cell and lymphoid tissue initiating cell development.
All of these lineages are thought to develop from a common lymphoid progenitor (CLP) suggesting that control of E2A activity may play a direct role in the lineage choice of the CLP. We have determined that E2A proteins are required for B-lymphocyte development in part because they induce the expression of EBF, another transcription factor that promotes B-lineage gene expression. In addition to its role in the regulation of EBF, we have shown that E2A proteins are required to maintain proliferation and survival of B-lymphocyte progenitors. E2A proteins are also required for proper T-lymphocyte development as demonstrated by the 5-fold decrease in T-lymphocyte progenitors in E2A-deficient mice. In addition, these mice succumb to T-lymphocyte progenitor lymphoma indicating that E2A proteins also function to suppress transformation in these cells.