Warmflash, Aryeh2024-05-222024-052024-04-19May 2024Kong, Xiangyu. Modeling human gastrulation at the extraemrbyonic-embryonic border. (2024). PhD diss., Rice University. https://hdl.handle.net/1911/116213https://hdl.handle.net/1911/116213EMBARGO NOTE: This item is embargoed until 2024-11-01Human gastrulation has long been a fascinating process that developmental biology tries to understand. Due to a lack of sample accessibility and ethical concerns, the answers to some basic questions like what signaling is initiating this process still elude us. In the past decade, several in vitro models were developed to answer such questions using human pluripotent stem cells (hPSCs), such as 2D and 3D human gastruloids. We gained a lot of insight into fate patterning, morphogenesis, and the mechanism driving them by studying these in vitro models. Compared to in vivo studies, these in vitro models provide us with better flexibility for experimental manipulation and scalability. However, the current in vitro models for human gastrulation are initiated by adding exogenous signaling molecules, by sticking to these systems, we risk missing some of the detailed dynamics during the process. It has long been hypothesized that the fate patterning during gastrulation is induced by signaling molecules secreted from the neighboring extraembryonic tissues, however, such inducing potency has yet to be reliably demonstrated in a human model. We developed a simple experimental model that juxtaposes extraembryonic and embryonic cells side by side to recreate a boundary to directly observe the interactions between them. We found that when hPSCs are juxtaposed against amnion-like cells (AMLCs), cells near the border recapitulating several aspects of gastrulation including…. We were able to capture this patterned differentiation and the underlying signaling in time. Studying the connection between said fate patterning and underlying signals grants us further insights into human gastrulation that have not been revealed in previous studies conducted on other model organisms or alternative gastrulation models. This demonstrates the potential of the juxtaposition model for studying the native signaling events between different cell populations.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.developmental biologystem cellsgastrulationpatterningThesis2024-05-22