Understanding Early Human Development Using Novel Single-Cell Technologies and Stem-Cell Based Embryo Models

To understand how cells in the early human embryo are controlled by gene expression programs would be instrumental for better understanding the causes of diseases and designing improved treatments. We have recently identified candidate transcription factors for the regulation of cell identity in each lineages of the early human embryo. We hypothesize that these candidate transcription factors are important to control cell identity in early human embryos. However, further studies are needed to elucidate the role of transcription factors in mediating the gene regulatory programs of human embryos. We will use imaging approaches to generate spatial maps of protein expression for candidate transcription factors, focusing on the placental progenitor cells of human embryos. We will then use single-cell multiome profiling, a method allowing the combined analysis of gene expression and accessible chromatin, to define the gene regulatory networks and regulatory elements involved in the formation of placental progenitor identity. We will study the effects of transcription factor knockout during induction of the placental progenitor program using human pluripotent stem cells. Furthermore, we will identify how modulating chromatin pathways affects cell fate and gene regulatory programs of early human embryos using chromatin remodeller inhibition combined with single-cell transcriptomics in stem cell-based human embryo models and human embryos. Altogether, we aim to better understand the effects of transcription factors and chromatin on gene expression programs, and ultimately gene regulation, cellular identity and diseases.

Keywords:Early human embryo development, Trophectoderm development, Pluripotent stem cells, Transcription factors, Single-cell gene regulatory networks

Disciplines:Stem cell biology