Can we steer how stem cells develop?

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Researchers at Johns Hopkins have found that a protein called Notch helps human embryonic stem cells decide their final fate, an important step towards stem cell treatments. The results were published in Cell Stem Cell.

Human embryonic stem cells receive signals from neighbouring cells telling them either to stay as stem cells or to turn into other types of cell, including the three layers that develop into an embryo, or the layer that becomes the placenta. Researchers have only just begun to understand the many signals involved.

"If you understand the mechanisms that control what the cells become, you open the door to many things," one of the researchers said: scientists could programme embryonic stem cells to replace cells a patient has lost to disease or injury.

The researchers grew human embryonic stem cells in the lab on a feeder layer of mouse cells that makes them multiply. Only a few stem cells had active Notch. When the researchers blocked the protein chemically, many more stem cells renewed themselves, suggesting Notch is needed for the cells to specialise, and that without it they stay unspecialised.

When the cells were made to specialise while Notch was blocked, they became placenta cells, but none of the three cell types that make up the embryo. So early placenta development doesn't need Notch, but Notch is needed for the cells to become embryonic cell types.

"We'd like to coax human embryonic stem cells into becoming blood stem cells, to develop treatments for patients who can't restore their blood cells," one researcher said. The team found that Notch can push embryonic stem cells to become blood cell precursors, which can turn into any type of blood cell, but not into nerve or liver cells. The study was funded by the National Institutes of Health and the Johns Hopkins Institute for Cell Engineering.

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