Transcriptome of mouse preimplantation development [C57BL/6 x Cast; WT]

Purpose: The goals of this study are to establish a dynamic roadmap of imprinted X chromosome inactivation and the role of Xist by elucidation of the transcriptome of Xist KO embryos during mouse preimplantation development Methods: mRNA profiles of the preimplantation embryos WT and KO for Xist were elucidated by RNA-seq at various stages. Trophoblasts isolated from blastocyst outgrowths were also included. The sequence reads that samples where gender could be determined and that passed quality filters were analyzed at the level of autosomes, X chromosome as well as single genes. Effects of genetic background on the kinetics of iXCI was evaluated by RNA-seq on E3.5 embryos with a hybrid C57BL/6 x Cast background. Results: Female embryos fail to silence the X chromosome at late preimplantation development. General autosomal gene expression is not affected in embryos lacking Xist. Conclusions: Xist is crucial for iXCI. In preimplantation embryos the main in vivo function of Xist is to regulate iXCI in females. Genetic background does not significantly influence kinetics of iXCI. Overall design: Global mRNA profiles of single preimplantation embryos were generated by deep sequencing.

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Wang F, Shin J, Shea JM, Yu J, Bošković A, Byron M, Zhu X, Shalek AK, Regev A, Lawrence JB, Torres EM, Zhu LJ, Rando OJ, Bach I