Human embryonic stem cells (hESCs) are conventionally derived from embryos that are at the blastocyst stage of development. Now, to gain insight into lineage allocation in early human development, Susan Fisher and colleagues report the derivation of various hESC lines using single blastomeres from 8- and 12-cell human embryos (p. 4010). The characterisation of these lines reveals that, at the transcriptome level, they differ from blastocyst-derived lines. Notably, blastomere-derived hESCs are enriched for genes expressed by trophoblasts and the ectoplacental cone. The researchers further show that blastomere-derived lines are hypomethylated in genomic regions that control trophoblast differentiation and early developmental processes, indicative of trophoblast competence. Variations in gene expression profiles are also observed among the various blastomere-derived lines (all of which are derived from embryos from a single couple), highlighting the existence of blastomere heterogeneity. In line with this, the authors show that levels of EOMES, T, GDF15 and active b-catenin differ among the blastomeres of 8- to 10-cell human embryos. Finally, the researchers report the derivation of the first human trophoblast stem cell line, which could be used in the future to model placental development and disorders.