Human life starts with a single cell that is formed by the fusion of the egg and the sperm. Within a week, the fertilized egg gives rise to a ball of cells containing "embryonic stem cells". Embryonic stem cells retain a unique ability to turn into all three distinct lineages that produce more than 200 cell types that make up the human bodies. Which genes in the human genome are essential for these transitions in cell identities during human development is largely unknown.
In this study, we focused on defining the genes critical for the development of the three major parts of the embryo, namely ectoderm, mesoderm and endoderm. Thus, using the cutting-edge CRISPR-based gene editing technology, we individually turned off nearly all protein-coding genes (more than 18,000 genes) in the human genome. Our analysis examined how each of these genes affect the transitions of human embryonic stem cells into the different embryonic germ layers.
These experiments enabled us to map all essential genes for the differentiation of human embryonic stem cells, laying out the cell signaling events and the regulatory genetic circuits of early human development. Interestingly, we showed a hierarchy among these essential genes for their role during embryonic development. The analysis permitted to analyze early phenotypes of all hereditary neurological diseases, demonstrating the growth defects of disorders such as microcephaly and autism during early embryogenesis.
Defining the genes essential for cell identities during differentiation of human embryonic stem cells should lead us to the generation of new media formulations for these cells. In addition, for the first time we have a comprehensive genomic view on early stages of human development. Our results can potentially also change the way we study human genetic disorders by focusing on their effects in early human embryogenesis.
Read the paper in the prestigious journal “Cell Stem Cell”.