Fuwa Takashi J, Kinoshita Takaaki, Nishida Hiroshi, Nishihara Shoko
Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan.
Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan.
Dev Biol. 2015 May 15;401(2):206-19. doi: 10.1016/j.ydbio.2015.03.003. Epub 2015 Mar 14.
Hematopoietic stem cells (HSCs) are present in hematopoietic organs and differentiate into mature blood cells as required. Defective HSCs have been implicated in the human autoimmune disease Tn syndrome, which results from the failure of the core 1 β1,3-galactosyltransferase 1 enzyme (C1β3GalT1) to synthesize T antigen. In both mice and humans, a reduced level of T antigen is associated with a reduction in blood cell numbers. However, the precise roles of T antigen in hematopoiesis are unknown. Here, we show that the Drosophila T antigen, supplied by plasmatocytes, is essential for the regulation of HSCs. T antigen appears to be an essential factor in maintaining the extracellular environment to support filopodial extensions from niches that are responsible for transmitting signaling molecules to maintain the HSCs. In addition, our results revealed that the clotting factor, hemolectin, disrupted the hemolymph environment of C1β3GalT1 mutants. This study identified a novel mucin function for the regulation of HSCs that may be conserved in other species.
造血干细胞(HSCs)存在于造血器官中,并根据需要分化为成熟血细胞。有缺陷的造血干细胞与人类自身免疫性疾病Tn综合征有关,该综合征是由核心1β1,3-半乳糖基转移酶1(C1β3GalT1)无法合成T抗原所致。在小鼠和人类中,T抗原水平降低均与血细胞数量减少有关。然而,T抗原在造血过程中的具体作用尚不清楚。在此,我们表明浆细胞提供的果蝇T抗原对于造血干细胞的调节至关重要。T抗原似乎是维持细胞外环境以支持龛的丝状伪足延伸的关键因素,这些龛负责传递信号分子以维持造血干细胞。此外,我们的结果显示凝血因子血凝集素破坏了C1β3GalT1突变体的血淋巴环境。这项研究确定了一种调节造血干细胞的新型粘蛋白功能,这种功能可能在其他物种中保守。