Sheng Zhong, UC San Diego - Friday January 23, 2015
- Single Cell Analysis of Cell Fate Decisions
Friday January 23rd at 11 am (Li Ka Shing Center, Room 130)
Sheng Zhong, Jacobs School of Engineering, UC San Diego
- 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 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. In addition, we initiated a class of statistical methods that simultaneously infer spatial and temporal groupings. Such methods explicitly model the time dependencies of clustering indices over time. Our method inferred three genes to be associated with the earliest cell fate decision, which was corroborated by experimental validations.