Person: Rao, Tirzah
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Rao
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Tirzah
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Rao, Tirzah
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Publication The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy(Nature Publishing Group, 2015) Wang, Leo; Rao, Tirzah; Rowe, Robert; Nguyen, Phi; Sullivan, Jessica; Pearson, Daniel; Doulatov, Sergei; Wu, Linwei; Lindsley, Robert; Zhu, Hao; DeAngelo, Daniel; Daley, George; Wagers, AmyMast cells are critical components of the innate immune system and important for host 48 defense, allergy, autoimmunity, tissue regeneration, and tumor progression.Dysregulated 49 mastcell development leads to systemic mastocytosis, a clinically variable but often 50 devastating family of hematologic disorders. Here we report that induced expression of 51 Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal 52 hematopoietic program, caused mast cell accumulation in adult mice in target organs such 53 as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid 54 commitment in LIN28B-‐expressing hematopoietic progenitors, with increased levels of 55 LIN28B in common myeloid and basophil-‐mast cell progenitors altering gene expression 56 patterns to favor cell fate choices that enhanced mast cell specification. In addition, 57 LIN28B-‐induced mast cells appeared phenotypically and functionally immature, and in 58 vitro assays suggested a slowing of mast cell terminal differentiation in the context of 59 LIN28B upregulation. Finally, interrogation of human mast cell leukemia samples revealed 60 upregulation of LIN28B in abnormal mast cells from patients with systemic mastocytosis 61 (SM). This work identifies Lin28 as a novel regulator of innate immune function and a new 62 protein of interest in mast cell disease.