Abstract
Trim27 (Zinc finger protein RFP) is a potential regulator of hematopoietic stem cells (HSC), yet its role in hematopoiesis remains elusive. Here, we investigated the roles of Trim27 in hematopoiesis by enforcing its expression in mouse and human hematopoietic stem and progenitor cells (HSPC). Ectopic expression of Trim27 in mouse fetal liver (FL) HSPC confers repopulating advantage with myeloid dominance. However, the number of HSC from Trim27 group was comparable with empty vector control group, indicating that overexpression of Trim27 unlikely expanded HSC. Transcriptome analysis of Trim27-overexpressing myeloid progenitor cells (MP) indicated that Trim27 up-regulated essential regulators of myelopoiesis, including Spi1 and Cebpg, up-regulated myeloid proliferation-related signaling genes Nras, Runx1, and Cbfb, up-regulated JAK/STAT signaling inhibitors Socs2, Socs3, and Cish, and up-regulated myeloid maturation-related genes Adam8 and Dek. Moreover, the myeloproliferative advantage caused by overexpressing Trim27/TRIM27 is conserved between mouse and human hematopoiesis. To our knowledge, this is the first study showing that Trim27 confers competitive hematopoiesis by promoting myeloid bias differentiation of HSPC, but not by expanding HSC.