ISBN: 1124718087 9781124718088

Category: Unavailable

Page count: 143

Current models of hematopoiesis are based on differentiation of multipotent progenitor cells into developmental intermediates of increasingly restricted developmental potential. Controlling this differentiation is a transcriptional network with signature patterns of gene expression characteristic of particular lineages. Within these networks, key transcription factors function to regulate induction of lineage specific genes as well as repress expression of genes associated with alternative cell fates. Key specification and commitment factors functioning in B and T cell development have been identified and studied for over a decade. To date, no transcriptional regulators have been identified that specify or commit progenitors to the natural killer (NK) cell lineage. Id2 is a transcription factor expressed very early in NK cell ontogeny and is required for the development of NK cells. Using expression of Id2 as a marker for development of the NK lineage, I sought to identify NK lineage specification or commitment factors. In this work, Ets1 was identified as a regulator of Idb2 expression. While previous work has described a role for Ets1 in development of NK cells, my analysis of Ets1 +/+ and Ets1-/- mice revealed a requirement for Ets1 in immature NK cells, much earlier than previously described. In addition, I found that Ets1 controls the expression of the NK transcriptome, as loss of Ets1 resulted in dysregulated expression of a large number of NK lineage associated genes. I also found that Ets1-/- NK cells display characteristics of spontaneous activation, indicating that Ets1 may have a role in repressing part of a terminal differentiation or activated effector gene program in NK cells.