Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm

Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.

Effects of Al^3+on pollutant removal and extracellular polymeric substances(EPS)under anaerobic,anoxic and oxic conditions

Aluminum ions produced by aluminum mining,electrolytic industry and aluminum-based coagulants can enter wastewater treatment plants and interact with activated sludge.They can subsequently contribute to the removal of suspended solids and affect activated sludge flocculation,as well as nitrogen and phosphorus removal.In this study,the effects of Al^3+on pollutant removal,sludge flocculation and the composition and structure of extracellular polymeric substances(EPS)were investigated under anaerobic,anoxic and oxic conditions.Results demonstrated that the highest chemical oxygen demand(COD)and total nitrogen(TN)removal efficiencies were detected for an Al^3+concentration of 10 mg/L.In addition,the maximal dehydrogenase activity and sludge flocculation were also observed at this level of Al^3+.The highest removal efficiency of total phosphorus(TP)was achieved at an Ar+concentration of30 mg/L.The flocculability of sludge in the anoxic zone was consistently higher than that in the anaerobic and oxic zones.The addition of Al^3+promoted the secretion of EPS.Tryptophan-like fluorescence peaks were detected in each EPS layer in the absence of Al^3+.At the Al^3+concentration of 10 mg/L,fulvic acid and tryptophan fluorescence peaks began to appear while the majority of protein species and the highest microbial activity were also detected.Low Al^3+concentrations(<10 mg/L)could promote the removal efficiencies of COD and TN,yet excessive Al^3+levels(>10 mg/L)weakened microbial activity.Higher Al^3+concentrations(>30 mg/L)also inhibited the release of phosphorus in the anaerobic zone by reacting with PO4^3-.

Genome transfer for the prevention of female infertility caused by maternal gene mutation

Poor oocyte quality is associated with early embryo developmental arrest and infertility.Maternal gene plays crucial roles in the regulation of oocyte maturation,and its mutation is a common cause of female infertility.However,how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive.Here,we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutationecaused female infertility.We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation(ZGA)during the maternal-zygotic transition.We next perform genome transfer at the oocyte(spindle transfer or polar body transfer)and zygote(early pronuclear transfer or late pronuclear transfer)stages to validate the feasibility of preventing Zar1 mutationecaused infertility.We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring.Moreover,those pups grow to adulthood and show normal fertility.Therefore,our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation.