ABSTRACT
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 EPS-blastoids 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.
Subject(s)
Pregnancy , Female , Animals , Mice , Tetraploidy , Blastocyst , Embryo, Mammalian , Cell Differentiation , Embryonic DevelopmentABSTRACT
Onset with fever and back pain, an 81-year-old man had sudden oliguria and progressively elevated serum creatine from normal range to 660 μmol/L within 1 week after receiving contrast agents, various antibiotics, and several nonsteroidal anti-inflammation drugs. Urine output recovered after supportive treatment. However, his serum creatinine level rose again soon after a temporary decline accompanied by gross hematuria with almost normal morphology, nephrotic proteinuria, and hypoalbuminemia. Renal biopsy revealed necrotizing glomerulonephritis. Methylprednisolone was intravenously administrated 500 mg per day for 3 days, followed by oral glucocorticoids and cyclophosphamide. Gradually the patient′s serum creatinine descended to 144 μmol/L.