Shaking up the salt and pepper: origins of cellular heterogeneity in the inner cell mass of the blastocyst

The inner cell mass (ICM) of the mammalian blastocyst contains pluripotent epiblast (EPI) and differentiating primitive endoderm (PE) cells, intermingled like salt and pepper. In mouse, the earliest known driver of EPI and PE cell fates is FGF4, but it was unclear whether cellular or molecular heterogeneity existed upstream of Fgf4. In a new study, published in the journal Nature Cell Biology, researchers in the lab of Takashi Hiiragi take us one step closer to understanding the origins of cellular heterogeneity in the ICM. Using single cell transcriptional profiling, Ohnishi and colleagues show that cellular heterogeneity is unlikely to precede the role of FGF4, and that FGF4 may help specify EPI as well as PE cell fates, providing exciting new insight into the origins of pluripotency.