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Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
Published on: February 22, 2016
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Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages
Yusuke Ohnishi1, Wolfgang Huber2, Akiko Tsumura3
1Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Nature Cell Biology
|December 3, 2013
Summary
Early mouse embryo development involves cell expression differences. Fibroblast growth factor 4 (Fgf4) drives the segregation of pluripotent epiblast (EPI) and primitive endoderm (PrE) lineages within the inner cell mass (ICM).
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Genomics
Background:
- Cellular heterogeneity is recognized as a precursor to lineage emergence in early mammalian embryos.
- Understanding the initial stages of lineage segregation in the inner cell mass (ICM) is crucial for developmental biology.
Purpose of the Study:
- To map the segregation of pluripotent epiblast (EPI) and primitive endoderm (PrE) lineages within the mouse blastocyst's ICM.
- To investigate the role of gene expression heterogeneity in early embryonic lineage specification.
Main Methods:
- Single-cell transcriptomic profiling of 66 individual ICM cells from mouse blastocysts.
- Clustering analysis to assess gene expression patterns and lineage relationships.
Main Results:
- Initially, ICM cells are transcriptionally indistinguishable.
- Lineage-specific markers show no correlation early in segregation, with hierarchy established later.
- Fibroblast growth factor 4 (Fgf4) displays bimodal expression and is essential for PrE and EPI differentiation.
Conclusions:
- Stochastic cell-to-cell expression heterogeneity, reinforced by signaling, drives ICM lineage segregation.
- Fgf4 acts as a key driver and requirement for the antagonistic separation of equivalent ICM cells into distinct lineages.
