Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos

TLDR

Mouse studies have informed early lineage decisions, yet comparable insights into human development remain scarce. The authors generated a comprehensive transcriptional atlas of human preimplantation embryos by sequencing 1,529 single cells from 88 embryos. This atlas was constructed using single‑cell RNA‑sequencing to map gene expression across individual cells. The data show that cells first co‑express lineage‑specific genes, then simultaneously differentiate into trophectoderm, epiblast, and primitive endoderm at blastocyst formation; female cells achieve X‑chromosome dosage compensation before implantation while XIST is expressed from both alleles and X‑linked genes remain biallelic during dampening, providing a valuable resource for future developmental and stem‑cell studies.

Abstract

Mouse studies have been instrumental in forming our current understanding of early cell-lineage decisions; however, similar insights into the early human development are severely limited. Here, we present a comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos. These data show that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in contrast to the mouse, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds. We envision broad utility of this transcriptional atlas in future studies on human development as well as in stem cell research.