Graduate Program in Molecular, Cellular and Integrative Bioscience.
Center for Molecular Immunology and Infectious Disease, and.
Blood Adv. 2019 Jul 23;3(14):2205-2217. doi: 10.1182/bloodadvances.2019000375.
Anemic stress induces the proliferation of stress erythroid progenitors in the murine spleen that subsequently differentiate to generate erythrocytes to maintain homeostasis. This process relies on the interaction between stress erythroid progenitors and the signals generated in the splenic erythroid niche. In this study, we demonstrate that although growth-differentiation factor 15 (Gdf15) is not required for steady-state erythropoiesis, it plays an essential role in stress erythropoiesis. Gdf15 acts at 2 levels. In the splenic niche, Gdf15 mice exhibit defects in the monocyte-derived expansion of the splenic niche, resulting in impaired proliferation of stress erythroid progenitors and production of stress burst forming unit-erythroid cells. Furthermore, Gdf15 signaling maintains the hypoxia-dependent expression of the niche signal, Bmp4, whereas in stress erythroid progenitors, Gdf15 signaling regulates the expression of metabolic enzymes, which contribute to the rapid proliferation of stress erythroid progenitors. Thus, Gdf15 functions as a comprehensive regulator that coordinates the stress erythroid microenvironment with the metabolic status of progenitors to promote stress erythropoiesis.
贫血应激会诱导小鼠脾脏中应激成红细胞祖细胞的增殖，随后这些祖细胞分化为红细胞以维持体内平衡。这个过程依赖于应激成红细胞祖细胞与脾脏成红细胞龛中产生的信号之间的相互作用。在这项研究中，我们证明了尽管生长分化因子 15（Gdf15）对于稳态红细胞生成不是必需的，但它在应激性红细胞生成中起着至关重要的作用。Gdf15 发挥了 2 个作用。在脾脏龛中，Gdf15 小鼠表现出单核细胞衍生的脾脏龛扩张缺陷，导致应激成红细胞祖细胞增殖受损和应激爆发生成单位-红细胞细胞生成减少。此外，Gdf15 信号维持了龛信号 Bmp4 的缺氧依赖性表达，而在应激成红细胞祖细胞中，Gdf15 信号调节代谢酶的表达，这有助于应激成红细胞祖细胞的快速增殖。因此，Gdf15 作为一种综合调节因子，协调应激性红细胞微环境与祖细胞的代谢状态，促进应激性红细胞生成。
