The unlimited self-renewal and developmental potential (or pluripotency) of human embryonic stem cells (hESCs) makes them an ideal source to generate desired cells and tissues to treat degenerative diseases. HESCs also represent a unique tool to study human development, given their direct inheritance from pre-implantation human embryo. The differences between human and other mammalian embryos identified so far further underscore the unprecedented values of hESCs. For example, leukemia inhibitory factor and bone morphogenetic proteins (BMPs) work in concert to sustain the pluriopotency of mouse, but not human, ES cells. Whereas, we have found that BMP4 causes hESC differentiation to trophoblast (Xu, et al., Nat. Biotech. 2002), the earliest differentiated cell type in mammalian embryos and essential for placental formation. We have further demonstrated that basic fibroblast growth factor (bFGF) synergizes with the BMP inhibitor Noggin to maintain the pluripotency of hESCs (Xu, et al. Nat. Methods, 2005). This discovery eliminates the need for animal feeder cells or any feeder-conditioned medium in hESC cultures. Based on these findings, we are currently interested in following lines of research.

Regulation of ES cell pluripotency by BMP/TGF-beta signaling. We like to analyze the genetic, epigenetic, and proteomic changes in hESCs in response to regulation of these signaling pathways. Understanding how hESCs retain and exit their pluripotent status and commit differentiated cell lineages is of great value. It could guide us to induce desired cell types from hESCs and develop new approaches to generating patient-tailored stem cells without concern for immunorejection and ethic issues. In addition, concepts learned from study of ES cell pluripotency may also apply to adult stem cells and cancer stem cells, and shed insight into how to induce endogenous adult stem cells to treat regenerative diseases while eliminating cancer stem cells.

Derivation of hESC lines with diverse genotypes including those associated to diseases.

As a State-funded stem cell core facility, our laboratory is charged to stock existing hESC lines, derive new hESC lines, and provide expertise and training on the scientifically and therapeutically important cells to interested researchers throughout Connecticut. The new hESC lines will be characterized for their genotypes with focus on disease-susceptible mutations, in hope to develop disease models for pathologic study, gene therapy, and drug screening. Overall, our laboratory is highly interested in conducting basic-to-translational research on hESCs, and promoting stem cell research in Connecticut by serving colleagues with our expertise.