Disease Focus: Fertility

Characterization and applications of human blastoids for understanding early human embryogenesis

Research Objective Our work will yield an improved stem-cell based embryo model that we will explore with various omics approaches and genetic screens to gain insights into the pathways that control human embryos. Impact An improved stem cell-based embryo model is a crucial step for in-depth studies of human development and will enhance our ability […]

Towards a trophectoderm stem-cell model representing human blastocysts of the highest implantation potential

Research Objective To define a new reference for embryos and stem cell lines of the highest developmental potential and work towards a trophoblast stem cell model to study factors important for successful implantation Impact The molecular determinants of successful human blastocyst implantation remain unknown and trophectoderm stem cell models to study these embryo factors and […]

Drivers of trophoblast stem/progenitor cell identity in human placenta

Research Objective This proposal will elucidate the mechanisms that identify a stem/progenitor cell population in the human placenta. Impact This proposal addresses our current knowledge gap on human placental development related to formation of the maternal/fetal interface during pregnancy, and placenta-associated pregnancy complications. Major Proposed Activities Identification of DNA regions, called enhancers, regulating placenta stem/progenitor […]

Human pluripotent stem cell-based therapeutics for preeclampsia

Preeclampsia (PE) is a pregnancy complication, characterized by high blood pressure and abnormal kidney function, which affects 5-8% of all pregnancies. It is responsible for a significant proportion of maternal deaths and growth-restricted babies; it is also a major reason why obstetricians induce delivery prematurely, resulting in additional neonatal complications, often requiring extended stays in […]

Correlated time-lapse imaging and single cell molecular analysis of human embryo development

We understand little about human development especially at the earliest stages. Yet human developmental biology is very important to stem cell biology and regenerative medicine for two reasons: 1) Understanding human developmental pathways especially of embryonic differentiation will inform our efforts to derive pluripotent stem cells and differentiate them to stable progenitors that are suitable […]

Molecular Mechanisms of Trophoblast Stem Cell Specification and Self-Renewal

Prematurity/preterm birth is the leading cause of neonatal death in the U.S. and in California. During an average day in California, 149 babies are born preterm. These babies are at increased risk for long-term disabilities, including cerebral palsy, gastrointestinal problems, and vision and hearing loss. Many premature babies also suffer from low birth weight, which […]

Derivation and comparative analysis of human pluripotent ESCs, iPSCs and SSCs: Convergence to an embryonic phenotype

This is an unprecedented time in stem cell biology and regenerative medicine. Today, we have cell lines and tools that did not exist just a few years ago. Indeed, human embryonic stem cells (hESCs) were derived from pre-implantation embryos just 10 years ago; more recently in the past year, cells with extensive similarities to ESCs […]

Human oocyte development for genetic, pharmacological and reprogramming applications

Trophoblast differentiation of human ES cells.

Human embryonic stem (ES) cells have the potential to form any cell type, but ironically, the first cell lineage to form during development still represents a surprising challenge. The first cell type to become specialized is an epithelial cell that later defines the boundary between the embryo and mother for the formation of the placenta. […]

Human Embryonic Stem Cell Differentiation to Trophoblast: Basic Biology and Clinical Translation to Improve Human Fertility

In addition to the important potential applications for transplantation and treatment of chronic diseases, human embryonic stem cells (hESC) are also a valuable resource to study early human development relevant to fertility and healthy pregnancies. After fertilization, the human zygote undergoes cell divisions and ultimately becomes the blastocyst that has an inner cell mass and […]