Wang Zhengqi, Kang Zizhen, Zhang Yi, Tse William, Bunting Kevin D
Aflac Cancer Center and Blood Disorders of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA.
Am J Stem Cells. 2012 Jun 30;1(2):146-153.
Interleukin (IL)-6 family cytokine signaling through gp130 and signal transducer and activator of transcription (STAT) activation is believed important for early hematopoiesis. To determine whether gp130/STAT1/3 physical interaction is required, we compared hematopoietic repopulating activities of embryonic day (E)14.5 fetal liver cells from gp130(FXXQ/FXXQ) knock-in mice, which have four mutated STAT1/3 binding sites. In hematopoietic cells, failure to tyrosine phosphorylate STAT3 by gp130 did not cause any significant effects on myeloid progenitor colony forming units (CFU) in vitro and or on competitive multilineage hematopoietic reconstitution. Serial transplantation of fetal liver (FL) cells was unaffected throughout primary, secondary, and tertiary transplants indicating normal self-renewal capacity. Even gp130(FXXQ/FXXQ) on the background of STAT5 deficiency, with known hematopoietic stem cell (HSC) repopulating dysfunction, did not further impair HSCs beyond that of STAT5 alone. Overall, the defective gp130-mediated STAT1/3 signaling is surprisingly dispensable for HSC function. However, since these mice lack both STAT1/3 binding sites there are several possible explanations for this result and these are discussed.
通过gp130以及信号转导和转录激活因子（STAT）激活的白细胞介素（IL）-6家族细胞因子信号传导被认为对早期造血作用至关重要。为了确定是否需要gp130/STAT1/3物理相互作用，我们比较了来自gp130（FXXQ/FXXQ）基因敲入小鼠胚胎第（E）14.5天胎肝细胞的造血重建活性，这些小鼠有四个突变的STAT1/3结合位点。在造血细胞中，gp130未能使STAT3酪氨酸磷酸化，对体外髓系祖细胞集落形成单位（CFU）以及竞争性多谱系造血重建均未产生任何显著影响。胎肝细胞的连续移植在原发性、继发性和三次移植过程中均未受影响，表明其具有正常的自我更新能力。即使在STAT5缺陷背景下的gp130（FXXQ/FXXQ），已知其造血干细胞（HSC）重建功能存在障碍，但除了STAT5单独存在时的影响外，并未进一步损害造血干细胞。总体而言，有缺陷的gp130介导的STAT1/3信号传导对于造血干细胞功能而言出人意料地并非必需。然而，由于这些小鼠同时缺乏STAT1/3结合位点，对于这一结果有几种可能的解释，本文将进行讨论。
