Bhandoola Lab Publishes in Nature Immunology
November 21, 2013
The lab of Avinash Bhandoola, MBBS, PhD, recently published a paper in Nature Immunology "T cell development requires constraint of the myeloid regulator C/EBP-a by the Notch target and transcriptional repressor Hes1." Notch signaling induces expression of genes that promote the maturation of T cells and discourage alternative cell fates. Hematopoietic deficiency in the Notch target Hes1 results in severe T cell lineage defects, but the underlying mechanism is unknown. The paper describes describes the mechanism of action of Hes1, a repressor protein that acts in the nucleus of immature T cells in the thymus. The Bhandoola lab found that Hes1 turns off genes such as C/EBPalpha, which promote the myeloid-cell fate and antagonize the T-cell fate. Whereas Hes1-deficient mice show severe T-cell defects, deleting the myeloid gene C/EBPalpha could restore normal T-cell development. This provides evidence that Hes1 keeps immature T cells on track by preventing them from defaulting to a myeloid developmental pathway, which controls non-lymphocyte cell maturation and establishes the importance of constraining myeloid developmental programs early in T-cell development, providing "clues about how to stop T-cell leukemias," as the first author states. Department faculty member Warren Pear, MD, PhD, is a co-author of the paper.
Read the Department of Communications news release.