Regulation of Fetal Hemoglobin Production in Humans.

摘要：出生前后胎儿血红蛋白表达降低是镰状细胞和地中海贫血综合征临床表现的决定性机制。因此，预防或逆转这一过程是治疗这些疾病的主要临床目标。在造血干细胞分化为红系祖细胞和前体细胞的过程中，胎儿血红蛋白的表达和调控是实验室正在进行的研究。几种方法被用来操纵胎儿血红蛋白的表达，包括信号转导、化学诱导和胎儿球蛋白基因的遗传调节。目前的焦点来自临床转录组研究，这些研究确定了let-7 microRNA可能参与胎儿血红蛋白的调节。目前，研究人员正在探索let-7 microRNA相关生物学，目的是开发治疗血红蛋白疾病的新疗法。

Summary: Decreased expression of fetal hemoglobin around the time of birth represents the defining mechanism in the clinical manifestation of sickle-cell and beta-thalassemia syndromes. Therefore, prevention or reversal of that process represents a major clinical goal for the treatment of those diseases. An ongoing interest of the laboratory involves the study of fetal hemoglobin expression and regulation as hematopoietic stem cells undergo differentiation to become erythroid progenitor and precursor cells. Several approaches are used to manipulate the expression of fetal hemoglobin including signal transduction, chemical induction, and genetic modulation of the fetal globin gene. A current focus arose from clinical transcriptome studies that identified the potential involvement of let-7 microRNA in the regulation of fetal hemoglobin. Studies are now underway to explore let-7 microRNA related biology with a goal of developing novel therapies for hemoglobin disorders.