Research on human pluripotent stem cells (hPSCs) has significant promise for regenerative medicine, disease modeling, and developmental biology studies. In this talk, I will discuss our effort in leveraging the mechanobiology of hPSCs in conjunction with some synthetic biomimetic systems to recapitulate and model human early embryonic development. I will first discuss our effort in constructing microengineered stem cell models of early human neurological developmental processes. Specifically, we have utilized microengineered hPSC cultures to develop autonomously regionalized neuroectoderm tissues in vitro. Importantly, our findings have suggested that induction and regionalization of neuroectoderm tissues involve mechanically gated molecular signaling (including Wnt, Hippo, and BMP) through regulations of cell shape and cytoskeleton contractility to reinforce spatial patterning of cell fates in neuroectoderm tissues. Together, our data provide strong evidence supporting critical involvements of cellular mechanics and mechanobiology as control mechanisms in ensuing robust formation of regionalized neuroectoderm tissues. In the last part of my talk, I will describe an efficient method to generate early human amniotic tissue in vitro through self-organized development of hPSCs in a bioengineered niche that mimics the in vivo implantation environment. Biophysical signals from the implantation-like niche act as a switch to toggle hPSC self-renewal versus amniogenesis. Our study unveils a self-organizing nature of human amniogenesis and establishes the first hPSC-based model system for investigating peri-implantation human amnion development.
Jianping Fu is an Associate Professor at the University of Michigan, Ann Arbor, with a primary appointment in the Mechanical Engineering Department and courtesy appointments in the Biomedical Engineering Department and the Cell and Developmental Biology Department. He also serves as the Associate Director for the Michigan Center for Integrative Research in Critical Care (MCIRCC) and is a Core Faculty Member for the UM Center for Organogenesis, the UM Comprehensive Cancer Center, and the UM Center for Systems Biology. Dr. Fu’s current research focuses on mechanobiology, stem cell biology, Bio-Microelectromechanical and -Nanoelectromechanical Systems (BioMEMS/NEMS), Lab-on-Chip (LOC), and applying microfabrication technology to illuminate biological systems at both the molecular and cellular levels. Dr. Fu is the recipient of the American Heart Association Scientist Development Award (2012), the National Science Foundation CAREER Award (2012), the Mechanical Engineering Outstanding Faculty Achievement Award (2014), the Robert M. Caddell Memorial Award for Research (2014), and the Ted Kennedy Family Team Excellence Award (2015). Dr. Fu's research group is currently supported by the National Science Foundation, the National Institutes of Health, the American Heart Association, and some other foundations and agencies.