Niels Geijsen, Ph.D.
Assistant Professor, Harvard Medical School
Harvard University
ngeijsen@mgh.harvard.edu

Geijsen Lab

Germ cells are perhaps the most interesting cells in our body since they are the only truly totipotent cells of our species. We are interested in the mechanism by which germ cells maintain their pristine state. In particular we are interested in the reprogramming of epigenetic information that occurs during germ cell development. In somatic cells, epigenetic control of gene expression limits a cell’s potential to transdifferentiate into cells of a different tissue type. Fusion of a somatic nucleus with embryonic germ cells or enucleated oocytes leads to reprogramming of the epigenetic information, resetting the cell to its totipotent state. This nuclear reprogramming holds the promise of novel cellular therapies for the treatment of degenerative disease, but little is known about the molecular mechanism mediating this phenomenon.

Germ cells undergo epigenetic reprogramming as part of their normal development and therefore the germ cell is the model system of choice for the investigation of the molecular mechanisms orchestrating this process. We have developed a system in which germ cell differentiation can be studied in vitro. Upon aggregation of embryonic stem (ES) cells into structures called embryoid bodies (EBs), ES cells differentiate to form ectoderm, endoderm and mesoderm derivatives as well as germ cells. Although EBs lack the spatial features found in early embryos, the cellular microenvironment surrounding the developing germ cells resembles that found during early embryonic development.

We are now using this system to analyze the molecular factors that control germ cell reprogramming. By manipulating the developing germ cells, or the stromal microenvironment surrounding them, we can analyze the effect of a variety of genes on epigenetic events such as histone modification and DNA methylation.

Selected Publications

Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, Daley GQ Nature 427: 148-154 (2004) Derivation of embryonic germ cells and male gametes from embryonic stem cells

Additional Publications

top