Jung Yusun, Kim Minsung, Soh Hyunsu, Lee Soyoung, Kim Jungtae, Park Surim, Song Kyuyoung, Lee Inchul
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
PLoS One. 2014 Jun 17;9(6):e100311. doi: 10.1371/journal.pone.0100311. eCollection 2014.
Hematopoiesis is a complex process requiring multiple regulators for hematopoietic stem/progenitor cells (HSPC) and differentiation to multi-lineage blood cells. TC1(C8orf4) is implicated in cancers, hematological malignancies and inflammatory activation. Here, we report that Tc1 regulates hematopoiesis in mice. Myeloid and lymphoid cells are increased markedly in peripheral blood of Tc1-deleted mice compared to wild type controls. Red blood cells are small-sized but increased in number. The bone marrow of Tc1-/- mice is normocellular histologically. However, Lin-Sca-1+c-Kit+ (LSK) cells are expanded in Tc1-/- mice compared to wild type controls. The expanded population mostly consists of CD150-CD48+ cells, suggesting the expansion of lineage-restricted hematopoietic progenitor cells. Colony forming units (CFU) are increased in Tc1-/- mice bone marrow cells compared to controls. In wild type mice bone marrow, Tc1 is expressed in a limited population of HSPC but not in differentiated cells. Major myeloid transcriptional regulators such as Pu.1 and Cebpα are not up-regulated in Tc1-/- mice bone marrow. Our findings indicate that TC1 is a novel hematopoietic regulator. The mechanisms of TC1-dependent HSPC regulation and lineage determination are unknown.
造血是一个复杂的过程，需要多种调节因子来调控造血干/祖细胞（HSPC）并使其分化为多谱系血细胞。TC1（C8orf4）与癌症、血液系统恶性肿瘤及炎症激活有关。在此，我们报告Tc1在小鼠中调节造血作用。与野生型对照相比，Tc1基因敲除小鼠外周血中的髓系细胞和淋巴细胞显著增加。红细胞体积小但数量增多。Tc1-/-小鼠的骨髓在组织学上细胞数量正常。然而，与野生型对照相比，Tc1-/-小鼠中Lin-Sca-1+c-Kit+（LSK）细胞增多。扩增的细胞群体主要由CD150-CD48+细胞组成，提示谱系受限的造血祖细胞发生扩增。与对照相比，Tc1-/-小鼠骨髓细胞中的集落形成单位（CFU）增加。在野生型小鼠骨髓中，Tc1在有限的HSPC群体中表达，但在分化细胞中不表达。主要的髓系转录调节因子如Pu.1和Cebpα在Tc1-/-小鼠骨髓中未上调。我们的研究结果表明，TC1是一种新型的造血调节因子。TC1依赖的HSPC调节及谱系决定机制尚不清楚。
