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Publication : Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing.

First Author  Biase FH Year  2014
Journal  Genome Res Volume  24
Issue  11 Pages  1787-96
PubMed ID  25096407 Mgi Jnum  J:355945
Mgi Id  MGI:7762037 Doi  10.1101/gr.177725.114
Citation  Biase FH, et al. (2014) Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing. Genome Res 24(11):1787-96
abstractText  It remains an open question when and how the first cell fate decision is made in mammals. Using deep single-cell RNA-seq of matched sister blastomeres, we report highly reproducible inter-blastomere differences among 10 2-cell and five 4-cell mouse embryos. Inter-blastomere gene expression differences dominated between-embryo differences and noise, and were sufficient to cluster sister blastomeres into distinct groups. Dozens of protein-coding genes exhibited reproducible bimodal expression in sister blastomeres, which cannot be explained by random fluctuations. The protein expression of one gene out of four of these bimodal genes tested, Gadd45a, exhibited clear inter-blastomeric contrasts. We traced some of the bimodal mRNA expressions to embryonic genome activation, and others to blastomere-specific RNA depletion. Inter-blastomere differences created coexpression gene networks that were much stronger and larger than those that can possibly be created by random noise. The highly correlated gene pairs at the 4-cell stage overlapped with those showing the same directions of differential expression between inner cell mass (ICM) and trophectoderm (TE). These data substantiate the hypothesis of inter-blastomere differences in 2- and 4-cell mouse embryos, and associate these differences with ICM/TE differences.
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