滋养层干细胞分化调节相关因子的研究进展

Novel Findings about the Factors Playing Roles in the Regulation of Trophoblast Stem Cells Differentiation

人类滋养层干细胞(TSC)来源于胚胎滋养外胚层,对胚胎命运起决定作用,已逐渐成为人类胎盘研究的热点。通过对小鼠胚胎的体外实验,已发现一些转录因子和蛋白调节因子在TSC状态的调节中发挥作用,比如转录调节相关因子FOS相关抗原1(FOSL1)、胎盘表达转录因子1(PLET-1)等,可促进TSC分化相关基因的表达,从而使TSC分化为不同滋养层细胞谱系;而蛋白调节因子如丝裂原活化蛋白激酶激酶4(MKK4)也可通过调节组蛋白去乙酰化酶6(HDAC6)进而介导上皮间质转化,促进TSC分化。综述近年发现的可调节TSC状态的相关转录因子、激酶与基因修饰酶类及蛋白调节因子的研究进展,为人类胎盘滋养层细胞分化相关妊娠疾病的防治提供必要的理论基础。

Human trophoblast stem cells(TSC),derived from the trophoblastic ectoderm,play a decisive role in the fate of embryos,and have gradually become a hot topic in the study of human placenta.Through in vitro experiments on mouse embryos,it has been found that some related transcription factors and protein regulatory factors play a role in the regulation of TSC state,such as the transcription regulatory factors FOS related antigen 1(FOSL1),placental expression transcription factor 1(PLET-1),etc.,can promote the expression of TSC differentiation related genes,so that TSC can differentiate into different trophoblast cell lineage;and protein regulatory factors such as mitogen-activated protein kinase kinase 4(MKK4)can also regulate histone deacetylase 6(HDAC6)to mediate epithelial stromal transformation and promote TSC differentiation.In this paper,we review the research progress of transcription factors,kinases,gene modifying enzymes and protein regulating factors that can regulate TSC status in recent years,and provide necessary theoretical basis for the prevention and treatment of pregnancy diseases related to the differentiation of human placental trophoblast cells.