Abstract

Bioengineered Human Embryo and Organ Models

Jianping Fu, Assistant Professor, University of Michigan

Early human development remains mysterious and difficult to study.  Recent advances in developmental biology, stem cell biology, and bioengineering have contributed to a significant interest in constructing controllable, stem cell-based models of human embryo and organs (embryoids / organoids).  The controllability and reproducibility of these human development models, coupled with the ease of genetically modifying stem cell lines, the ability to manipulate culture conditions and the simplicity of live imaging, make them robust and attractive systems to disentangle cellular behaviors and signaling interactions that drive human development.  In this talk, I will describe our effort in using human pluripotent stem cells (hPSCs) and bioengineering tools to develop controllable models of the peri-implantation embryonic development and early neural development.  The peri-implantation human embryoids recapitulate early post-implantation developmental landmarks successively, including amniotic cavity formation, amniotic ectoderm-epiblast patterning, primordial germ cell specification, development of the primitive streak, and yolk sac formation.  I will further discuss an hPSC-based, microfluidic neural tube-like structure (or µNTLS), whose development recapitulates some critical aspects of neural patterning in both brain and spinal cord regions and along both rostral-caudal and dorsal-ventral axes.  The µNTLS is further utilized for studying development of different neuronal lineages, revealing pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and caudal gene CDX2 in spinal cord and trunk neural crest development.  We have further developed dorsal-ventral patterned, microfluidic forebrain-like structures (µFBLS) with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic human embryonic brain development in pallium and subpallium areas, respectively.  Together, both µNTLS and µFBLS offer 3D lumenal tissue architectures with an in vivo-like spatiotemporal cell differentiation and organization, useful for studying human neurodevelopment and disease.