Tracking stem cell reprogramming: Biologists reveal genes key to development of pluripotency, in single cells

ScienceDaily (Sep. 13, 2012) Several years ago, biologists discovered that regular body cells can be reprogrammed into pluripotent stem cells -- cells with the ability to become any other type of cell. Such cells hold great promise for treating many human diseases.

These induced pluripotent stem cells (iPSCs) are usually created by genetically modifying cells to overexpress four genes that make them revert to an immature, embryonic state. However, the procedure works in only a small percentage of cells.

Now, new genetic markers identified by researchers at MIT and the Whitehead Institute could help make that process more efficient, allowing scientists to predict which treated cells will successfully become pluripotent.

The new paper, published in the Sept. 13 online edition of Cell, also identifies new combinations of reprogramming factors that produce iPSCs, according to the researchers.

Led by Rudolf Jaenisch, an MIT professor of biology and member of the Whitehead Institute, the study is the first to examine genetic changes that occur in individual cells as they become pluripotent. Previous studies have only looked at gene-expression changes in large populations of cells -- not all of which will actually reprogram -- making it harder to pick out genes involved in the process.

"In previous studies, you weren't able to detect the few cells that expressed predictive pluripotency markers. The really cool part of this study is that you can detect two or three cells that express these important genes early, which has never been done before," says Dina Faddah, a graduate student in Jaenisch's lab and one of the paper's lead authors.

The other lead author is Yosef Buganim, a postdoc at the Whitehead Institute.

Single-cell analysis

In 2007, scientists discovered that adult human cells could be reprogrammed by overexpressing four genes -- Oct4, Sox2, c-Myc and Klf4. However, in a population of cells in which those genes are overexpressed, only about 0.1 to 1 percent will become pluripotent.

In the new study, Jaenisch's team reprogrammed mouse embryonic fibroblast cells and then measured their expression of 48 genes known or suspected to be involved in pluripotency at several points during the process. This allowed them to compare gene-expression profiles in cells that became pluripotent, those that did not, and those that were only partially reprogrammed.

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Tracking stem cell reprogramming: Biologists reveal genes key to development of pluripotency, in single cells