Niels Geijsen, Ph.D.
Assistant Professor of Medicine, Harvard Medical School
Pluripotent stem cells are characterized by their ability to propagate indefinitely in vitro, while retaining the ability to differentiate into derivatives of the three germ layers; endoderm, mesoderm and ectoderm. The first description of the derivation of pluripotent stem cells was two independent reports by Gail Martin and Martin Evans describing the derivation of murine embryonic stem cells (ES cells) from pre-implantation blastocyst embryos. Since their first discovery, murine ES cells have been instrumental in analyzing gene function in mammalian development and disease.
With the derivation of human ES cells it was anticipated that these cells would similarly expedite our understanding and treatment of human disease. Yet, in comparison to their murine counterparts, human ES cells are relatively difficult to propagate, manipulate and differentiate. The generation of recombinant human cell lines has proven to be cumbersome, and to date only a handful of mutant- or reporter cell lines have been described. As a result, progress in the application of human ES cells in drug discovery and cell based therapies has been slow.
Since human ES cells were long thought to be the Homo Sapiens equivalent of murine ES cells, the above differences between these cell types were largely contributed to species-specific stem cell traits. We recently reported that the remarkable properties of murine ES cells such as their ability to form chimeras are in part a consequence of the growth factor conditions in which these cells are maintained (LIF and BMP4). When murine stem cells are instead maintained under human ES cell culture conditions (bFGF), the cells display morphological- and molecular characteristics of human ES cells and adopt many of the fickle characteristics that appear intrinsic to human ES cells.
Our future work is aimed at understanding the molecular mechanisms that define the different stem cell states, with a particular interest in exploring how the (micro) environment controls the stem cell’s functional properties. With this knowledge, we aim to develop novel human models for development and disease, to ultimately enable the application of cell- or tissue based therapies for the treatment of degenerative disease.
May Chen, PhD
Chou, Y.F., Chen, H.H., Eijpe, M., Yabuuchi, A., Chenoweth, J.G., Tesar, P., Lu, J., McKay, R.D., and Geijsen, N. 2008. The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells. Cell135(3): 449-461.
Geijsen, N., Horoschak, M., Kim, K., Gribnau, J., Eggan, K., and Daley, G.Q. 2004. Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature427(6970): 148-154.