Derivation of human primordial germ cell-like cells in an embryonic-like culture.

Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution.

Mechanosensitive Channel-Based Optical Membrane Tension Reporter.

Plasma membrane tension functions as a global physical organizer of cellular activities. Technical limitations of current membrane tension measurement techniques have hampered in-depth investigation of cellular membrane biophysics and the role of plasma membrane tension in regulating cellular processes. Here, we develop an optical membrane tension reporter by repurposing an mechanosensitive channel via insertion of circularly permuted GFP (cpGFP), which undergoes a large conformational rearrangement associated with channel activation and thus fluorescence intensity changes under increased membrane tension.

Single-cell analysis of embryoids reveals lineage diversification roadmaps of early human development.

Despite its clinical and fundamental importance, our understanding of early human development remains limited. Stem cell-derived, embryo-like structures (or embryoids) allowing studies of early development without using natural embryos can potentially help fill the knowledge gap of human development. Herein, transcriptome at the single-cell level of a human embryoid model was profiled at different time points.

Micro/nanoengineered technologies for human pluripotent stem cells maintenance and differentiation.

Human pluripotent stem cells (hPSCs) are a promising source of cells for cell replacement-based therapies as well as modeling human development and diseases . However, achieving fate control of hPSC with a high yield and specificity remains challenging. The fate specification of hPSCs is regulated by biochemical and biomechanical cues in their environment.

Machine learning-assisted imaging analysis of a human epiblast model.

The human embryo is a complex structure that emerges and develops as a result of cell-level decisions guided by both intrinsic genetic programs and cell-cell interactions. Given limited accessibility and associated ethical constraints of human embryonic tissue samples, researchers have turned to the use of human stem cells to generate embryo models to study specific embryogenic developmental steps. However, to study complex self-organizing developmental events using embryo models, there is a need for computational and imaging tools for detailed characterization of cell-level dynamics at the single cell level.

Branching development of early post-implantation human embryonic-like tissues in 3D stem cell culture.

Human embryonic stem cells (hESCs) have the intrinsic capacity to self-organize and generate patterned tissues. In vitro models that coax hESCs to form embryonic-like structures by modulating physical environments and priming with chemical signals have become a powerful tool for dissecting the regulatory mechanisms underlying early human development. Here we present a 3D suspension culture system of hESCs that can generate post-implantation, pre-gastrulation embryonic-like tissues in an efficient and controllable manner.

Bioengineered pluripotent stem cell models: new approaches to explore early human embryo development.

Human development is a complex process in which environmental signals and factors encoded by the genome interact to engender cell fate changes and self-organization that drive the progressive formation of the human body. Herein, we discuss engineered biomimetic platforms with controllable environments that are being used to develop human pluripotent stem cell (hPSC)-based embryo models (or embryoids) that recapitulate a wide range of early human embryonic developmental events. Coupled with genome editing tools, single-cell analysis, and computational models, they can be used to parse the spatiotemporal dynamics that lead to differentiation, patterning, and growth in early human development.

Microengineered human amniotic ectoderm tissue array for high-content developmental phenotyping.

During early post-implantation human embryogenesis, the epiblast (EPI) within the blastocyst polarizes to generate a cyst with a central lumen. Cells at the uterine pole of the EPI cyst then undergo differentiation to form the amniotic ectoderm (AM), a tissue essential for further embryonic development. While the causes of early pregnancy failure are complex, improper lumenogenesis or amniogenesis of the EPI represent possible contributing factors.

Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells.

Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo.