Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages.


Publication Type:

Source:

Nat Cell Biol, Volume 16, Issue 1, p.27-37 (2014)

Keywords:

Animals, Biomarkers, Blastocyst Inner Cell Mass, Cell Lineage, Cell Separation, Endoderm, Fibroblast Growth Factor 4, Gene Expression Profiling, Gene Expression Regulation, Developmental, Germ Layers, Mice, Models, Biological, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Principal Component Analysis, Signal Transduction, Single-Cell Analysis

Abstract:

<p>It is now recognized that extensive expression heterogeneities among cells precede the emergence of lineages in the early mammalian embryo. To establish a map of pluripotent epiblast (EPI) versus primitive endoderm (PrE) lineage segregation within the inner cell mass (ICM) of the mouse blastocyst, we characterized the gene expression profiles of individual ICM cells. Clustering analysis of the transcriptomes of 66 cells demonstrated that initially they are non-distinguishable. Early in the segregation, lineage-specific marker expression exhibited no apparent correlation, and a hierarchical relationship was established only in the late blastocyst. Fgf4 exhibited a bimodal expression at the earliest stage analysed, and in its absence, the differentiation of PrE and EPI was halted, indicating that Fgf4 drives, and is required for, ICM lineage segregation. These data lead us to propose a model where stochastic cell-to-cell expression heterogeneity followed by signal reinforcement underlies ICM lineage segregation by antagonistically separating equivalent cells.</p>