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Mol Syst Biol ; 14(9): e8140, 2018 09 03.
Article in English | MEDLINE | ID: mdl-30177503

ABSTRACT

It is well known that clonal cells can make different fate decisions, but it is unclear whether these decisions are determined during, or before, a cell's own lifetime. Here, we engineered an endogenous fluorescent reporter for the pluripotency factor OCT4 to study the timing of differentiation decisions in human embryonic stem cells. By tracking single-cell OCT4 levels over multiple cell cycle generations, we found that the decision to differentiate is largely determined before the differentiation stimulus is presented and can be predicted by a cell's preexisting OCT4 signaling patterns. We further quantified how maternal OCT4 levels were transmitted to, and distributed between, daughter cells. As mother cells underwent division, newly established OCT4 levels in daughter cells rapidly became more predictive of final OCT4 expression status. These results imply that the choice between developmental cell fates can be largely predetermined at the time of cell birth through inheritance of a pluripotency factor.


Subject(s)
Cell Differentiation/genetics , Cell Tracking/methods , Human Embryonic Stem Cells/metabolism , Inheritance Patterns , Octamer Transcription Factor-3/genetics , Pluripotent Stem Cells/metabolism , Bone Morphogenetic Protein 4/pharmacology , CDX2 Transcription Factor/genetics , CDX2 Transcription Factor/metabolism , CRISPR-Cas Systems , Cell Cycle/genetics , Gene Expression Regulation , Genes, Reporter , Human Embryonic Stem Cells/cytology , Humans , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Octamer Transcription Factor-3/metabolism , Pluripotent Stem Cells/cytology , Protein Engineering/methods , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Signal Transduction , Single-Cell Analysis/methods , Red Fluorescent Protein
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