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

作者：Sophie Petropoulos, Daniel Edsgärd, Björn Reinius, Qiaolin Deng, Sarita Panula, Simone Codeluppi, Álvaro Plaza Reyes, Sten Linnarsson, Rickard Sandberg, Fredrik Lanner · 发表于：Cell · 年份：2016 · DOI：10.1016/j.cell.2016.03.023 · 被引用次数：1153 · 研究领域：Pluripotent Stem Cells Research、CRISPR and Genetic Engineering、MicroRNA in disease regulation

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.