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.

Porcine pluripotent stem cells: progress, challenges and prospects

Pluripotent stem cells(PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scienti?c and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.