We carried out DNA microarray-based global expression profiling of all preimplantation stages in mouse. It revealed and characterized the distinctive patterns of maternal RNA degradation and two major transient waves of de novo transcription: zygotic genome activation (ZGA) and mid-preimplantation gene activation (MGA). We also developed a technique to do large-scale Whole Mount In Situ Hybridization (WISH), which allows us to reveal the spatial expression patterns of 91 genes in mouse preimplantation embryos. Through these analyses, we identified a number of genes that show unique expression patterns. We have demonstrated that one of them, named Zscan4, is expressed exclusively in 2-cell mouse embryos and ES cells and plays a critical role in the progression of preimplantation development. We also identified genes, named Trim43a, Trim43b, and Trim43c, whose expression began at the 2-cell stage, peaked at the 8-cell/morula stage, and dramatically fell by the blastocyst stage. We are currently investigating whether Zscan4 overexpression can increase the potency of ES cells by injecting Zscan4-manipulated ES cells into mouse blastocysts.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000655-12
Application #
8148279
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2010
Total Cost
$541,369
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Amano, Tomokazu; Hirata, Tetsuya; Falco, Geppino et al. (2013) Zscan4 restores the developmental potency of embryonic stem cells. Nat Commun 4:1966
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Xie, Huirong; Sun, Xiaofei; Piao, Yulan et al. (2012) Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem 287:32288-97
Hammachi, Fella; Morrison, Gillian M; Sharov, Alexei A et al. (2012) Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency. Cell Rep 1:99-109
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Kim, Youngjo; Sharov, Alexei A; McDole, Katie et al. (2011) Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. Science 334:1706-10
Zalzman, Michal; Falco, Geppino; Sharova, Lioudmila V et al. (2010) Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 464:858-63
Sharov, Alexei A; Piao, Yulan; Ko, Minoru S H (2010) Gene expression profiling of mouse embryos with microarrays. Methods Enzymol 477:511-41

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