New stem cell maintenance protein found

November 30, 2002

Scientists have identified a critical, new stem cell protein - a marked advance in the elucidation of the molecular blueprint of stem cells.

Drs. Robert Tsai and Ronald McKay at the NIH have discovered a novel gene, called nucleostemin, whose encoded protein is necessary for maintaining the proliferative capacity of embryonic and adult stem cells, and possibly some types of cancer cells. Their report is published in the December 1 issue of the scientific journal Genes & Development.

Embryonic stem cells are pluripotent progenitor cells that can differentiate into all of the cell types of the body. Adult stem cells, in contrast, have a less versatile potential: Their differentiation is generally restricted to the cell types of a specific tissue (although recent work has expanded the previously known range of adult stem cell differentiation potential).

A key feature of both embryonic and adult stem cells is their capacity for self-renewal as well as differentiation - ensuring that a constant pool of undifferentiated stem cells always exists. Drs. Tsai and McKay have identified nucleostemin as a critical regulator of this delicate balance.

Drs. Tsai and McKay originally identified nucleostemin as a protein abundantly expressed in rat CNS (central nervous system) stem cells that is markedly down-regulated during differentiation, suggesting a possible role in stem cell maintenance. The researchers went on to show that nucleostemin is expressed in various adult and embryonic stem cell populations, as well as in some human cancer cell lines, and that its expression is consistently turned-off during the differentiation of stem cells into more specialized cell types.

Using the RNAi gene silencing method, Drs. Tsai and McKay disrupted normal nucleostemin expression patterns in rodent CNS stem cells and human osteosarcoma cancer cells. They found that the aberrant down-regulation of nucleostemin in these cells caused a decrease in cell proliferation, suggesting that the expression of nucleostemin is required for stem cell -- and some cancer cell -- proliferation.

Although the precise mechanism of nucleostemin action is not yet fully understood, the identification of a gene whose protein product specifically promotes the proliferation of stem cells and some cancer cells has important clinical implications for both the use of stem cells in regenerative medicine as well as the treatment of cancer. As Dr. Tsai explains, "The characterization of nucleostemin suggests that a unique primitive state is shared by both stem cells and cancer cell lines. The identification of common molecules shared by both stem cells and cancer cells may facilitate the discovery of self-renewing populations within a given tumor by evaluating their expression levels. Perhaps, in the future, targeting these cells will achieve a better therapeutic outcome."
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Cold Spring Harbor Laboratory

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