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The first two blastomeres contribute unequally to the human embryo
Introduction
Results
Lineage tracing of human 2-cell stage blastomeres
2-cell stage human blastomeres contribute unequally to ICM, EPI, and polar TE
2-cell clonal imbalance is not explained by blastomere arrest or genomic instability
Live imaging reveals that asymmetric cell divisions at the 8-cell stage predict ICM composition
A computational model of three parameters predicts clonal imbalance in human blastocysts
Lineage tracing of time-lapse movies reveals clonal imbalances at the 8-to-16-cell division in human embryos
The faster-dividing 2-cell stage blastomere is biased toward the first ACD at the 8-cell stage
Discussion
Limitations of the study
Supplemental information
Acknowledgments
Author contributions
Declaration of interests
References
STAR★Methods
Key resources table
Resource availability
Lead contact
Materials availability
Data and code availability
Experimental model and study participant details
Mouse embryo recovery and culture
Human embryo recovery and culture
Embryoscope™ time-lapse movies
Method details
Microinjection of mGap43-GFP mRNA for cell and lineage labelling
Fixation and staining
Live staining with SiR-Actin and SPY555-DNA dyes
Time-lapse live imaging
Human blastocyst ploidy analysis
Quantification and statistical analysis
Embryo exclusion criteria
Number of GFP+ and GFP- cells in the human blastocysts
Scoring of blastocysts using the Gardner and Schoolcraft blastocyst grading system
3D projections of human blastocysts
Lineage tracing of the human embryo
Angle of cell division
Number, position and borders of clone clusters in trophectoderm
Clonal composition of the polar vs mural TE
Cell cycle length
Lineage tree reconstructions from 1- to 16-cell stage using Embryoscope™ time-lapse movies
Detection of the presence of arrested blastomeres
Statistical model of blastocyst development with random cell arrest, death and internalization
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