Barbarani Gloria, Labedz Agata, Stucchi Sarah, Abbiati Alessia, Ronchi Antonella E
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
Front Cell Dev Biol. 2021 Apr 1;9:640060. doi: 10.3389/fcell.2021.640060. eCollection 2021.
The expression of the fetal Gγ- and Aγ-globin genes in normal development is confined to the fetal period, where two γ-globin chains assemble with two α-globin chains to form αγ tetramers (HbF). HbF sustains oxygen delivery to tissues until birth, when β-globin replaces γ-globin, leading to the formation of αβ tetramers (HbA). However, in different benign and pathological conditions, HbF is expressed in adult cells, as it happens in the hereditary persistence of fetal hemoglobin, in anemias and in some leukemias. The molecular basis of γ-globin differential expression in the fetus and of its inappropriate activation in adult cells is largely unknown, although in recent years, a few transcription factors involved in this process have been identified. The recent discovery that fetal cells can persist to adulthood and contribute to disease raises the possibility that postnatal γ-globin expression could, in some cases, represent the signature of the fetal cellular origin.
在正常发育过程中，胎儿Gγ-和Aγ-珠蛋白基因的表达仅限于胎儿期，在此期间，两条γ-珠蛋白链与两条α-珠蛋白链组装形成αγ四聚体（HbF）。HbF维持向组织输送氧气直至出生，此时β-珠蛋白取代γ-珠蛋白，导致形成αβ四聚体（HbA）。然而，在不同的良性和病理条件下，HbF在成体细胞中表达，如胎儿血红蛋白遗传性持续存在、贫血和某些白血病的情况。尽管近年来已经鉴定出一些参与此过程的转录因子，但胎儿期γ-珠蛋白差异表达及其在成体细胞中不适当激活的分子基础在很大程度上仍不清楚。最近发现胎儿细胞可存活至成年并导致疾病，这增加了一种可能性，即在某些情况下，出生后γ-珠蛋白的表达可能代表胎儿细胞起源的特征。
