The transcriptional activator Klf5 recruits p300-mediated H3K27ac for maintaining trophoblast stem cell pluripotency

The effective proliferation and differentiation of trophoblast stem cells(TSCs)is indispensable for the development of the placenta,which is the key to maintaining normal fetal growth during pregnancy.Kruppel-like factor 5(Klf5)is implicated in the activation of pluripotency gene expression in embryonic stem cells(ESCs),yet its function in TSCs is poorly understood.Here,we showed that Klf5 knockdown resulted in the downregulation of core TSC-specific genes,consequently causing rapid differentiation of TSCs.Consistently,Klf5-depleted embryos lost the ability to establish TSCs in vitro.At the molecular level,Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes.Deprivation of Klf5 impaired the enrichment of p300,a major histone acetyl transferase of H3 lysine 27 acetylation(H3K27ac),and further reduced the occupancy of H3K27ac at promoter regions,leading to decreased transcriptional activity of TSC pluripotency genes.Thus,our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs and provide a reference for understanding placental development and improving pregnancy rates.

Frontier Progress in the Establishment of Trophoblast Stem Cell and the Identification of New Cell Subtypes at the Maternal-Fetal Interface

Proper development of the human placenta is of vital importance for a successful pregnancy,and a series of pregnancy complications are considered originating from dysfunctional placentas.Like other organ system development,placentation requires large numbers of co-regulators,while the underlying molecular mechanisms orchestrating the placental formation and function are poorly understood.Although we have made many signs of progress in understanding the placental architectures and developments using mouse models,the species-specific differences impede our progress due to the lack of appropriate model systems.In the past few years,major progress has been made by the establishment of novel in-vitro self-renewing stem cell models,as well as identifying the full picture of the cellular organization of the maternal and fetal interface.Providing the tools for the investigation of placentation and reproductive-related regulation mechanism.In this review,we focus on the detailed progress of the human trophoblast stem cells culturing system,and the cellular and molecular terrain at the maternal-fetal interface,respectively,thus providing new insights into placental development.