Methods and Materials for Controlling Stem Cell and Cancer Cell Proliferation and Differentiation

This work describes a novel nucleolar mechanism that controls the cell-cycle progression in CNS stem cells and cancer cells. The inventors identified a novel peptide, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other stem cell-enriched populations. When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo. Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells.

Nucleic acids encoding the polypeptide, vectors incorporating the nucleic acids, and host cells transfected with these nucleic acids are disclosed and claimed. The claimed invention includes methods for regulating cell differentiation, cell proliferation, or both using nucleostemin. Methods for inducing differentiation, inhibiting proliferation, and inducing senescence of a cell by altering the level of a nucleostemin polypeptide and related amino acid sequences are disclosed and claimed. Methods for screening for agents that affect proliferation, differentiation, or senescence of cells are also disclosed and claimed. Further information can be found in Genes Dev. 2002 Dec 1;16 (23):2991-3003.