Molecular mechanism underlying cell identity and lineage choices in mammalian early embryonic development

The first lineage choice in human embryo development extra- and embryonic cell fates.

Extraembryonic trophectoderm (TE) gives rise to placental tissues while the inner cell mass (ICM) progresses via the epiblast stage to form the fetus.

The restriction of ICM cells to embryonic lineage capacity is crucial for ordered embryonic development, and concomitant development of extraembryonic support tissue from TE is crucial for survival of the embryo.

These earliest steps are remarkably inefficient in humans: it is estimated that only one in three conceptions progress to live birth, with an early time window before and after implantation being the most crucial stages for a successful pregnancy.

The aim of this project is to elucidate the mechanisms of the first cell fate decision and subsequent lineage determination by employing in vitro preimplantation models based on naïve human embryonic stem cells and 3D blastoids.

The project will rely on quantitative epigenome profiling technology, functional perturbations, live cell imaging, and single-cell multimodal readouts to capture complex regulatory networks at play during early human development.

We will more broadly elucidate how chromatin makeup dynamically changes as a function of the cell cycle and how cells integrate internal and external information to make cell fate decisions.

Our research will further technology for dissecting complex developmental programs and provide insights into early human development and fertility.