Germline stem (GS) cells can only differentiate into germline cells, while multipotent germ stem (mGS) cells, like embryonic stem (ES) cells, can differentiate into various somatic cells and tissues. The proteomic profiles in GS and mGS cells were compared by two-dimensional gel electrophoresis. Ten down-regulated and 16 up-regulated proteins were differentially expressed in mGS cells in comparison to GS cells, and these proteomic characteristics were very much similar to those in ES cells indicating that multipotency of mGS and ES cells is based on a common molecular event(s). Protein identification by mass spectrometry revealed that these proteins were functionally involved in cell signaling, transcription factors, metabolism, and protein folding. The identified proteins in the present study may thus reveal its biological characteristics and functional property in self-renewal and multipotency. (c) 2006 Elsevier Inc. All rights reserved.