Nuclear proteomics and directed differentiation of embryonic stem cells.

During the past decade, regenerative medicine has been the subject of intense interest due, in large part, to our growing knowledge of embryonic stem (ES) cell biology. ES cells give rise to cell lineages from the three primordial germ layers--endoderm, mesoderm, and ectoderm. This process needs to be channeled if these cells are to be differentiated efficiently and used subsequently for therapeutic purposes. Indeed, an important area of investigation involves directed differentiation to influence the lineage commitment of these pluripotent cells in vitro. Various strategies involving timely growth factor supplementation, cell co-cultures, and gene transfection are used to drive lineage specific emergence. The underlying goal is to control directly the center of gene expression and cellular programming--the nucleus. Gene expression is enabled, managed, and sustained by the collective actions and interactions of proteins found in the nucleus--the nuclear proteome--in response to extracellular signaling. Nuclear proteomics can inventory these nuclear proteins in differentiating cells and decipher their dynamics during cellular phenotypic commitment. This review details what is currently known about nuclear effectors of stem cell differentiation and describes emerging techniques in the discovery of nuclear proteomics that will illuminate new transcription factors and modulators of gene expression.