Friday, 12 April 2013

Researchers isolate, for the first time, mammary gland stem cells of unprecedented purity

In a new study, researchers from the laboratory of Professor Gregory Hannon at Cold Spring Harbor Laboratory seem to have solved a long-standing problem, isolating pure mammary gland stem cells. These cells are invaluable in understanding breast cancer and could help in the development of new drugs against the disease.

In their press release, the researchers explain that isolating stem cells is a lot like "fishing". All you need is the correct "hook" that recognises specific proteins on the surface of the desired cell in order to pull it out. As of today, researchers didn't have the correct "hook" for mammary gland stem cells (MaSCs) and as a result they could not extract pure MaSCs populations. Still, even partially purified stem cell populations were enough to improve our current understanding of breast tumorigenesis.

Image of a healthy and a cancerous breast (mammogram)
Mammograms showing a healthy breast (left) and a cancerous breast (right).

In this study, the researchers have identified a surface marker, called Cd1d, that exists on the surface of mouse MaSCs. With the help of this marker the researchers managed, for the first time, to create a highly purified MaSCs sample. The good thing about this marker is that it is expressed by human mammary cells, meaning that these cells can be isolated by human tissue as well.

To isolate the marker, the scientists took advantage of a trait that MaSCs have, dividing slower than other cells do. Then, they used a special strain of mouse that expresses a green fluorescent protein (GFP), in a subtype of epithelial cells that was known to include MaSCs. Next, they exploited another "trick",  the ability to deactivate the GFP gene by feeding the mice a chemical called doxycycline. Camila Dos Santos, study's first author explains:

"The beauty of this model is that by stopping GFP expression, you can directly measure the number of cell divisions that have happened since GFP was turned off," 

"The cells that divide the least will carry GFP the longest and are the ones we characterised."

The researchers say that their MaSCs purification method easily surpasses any other previously described adding that it can be a valuable tool in the battle against breast cancer.

"With this advancement, we are now able to profile normal and cancer stem cells at a very high degree of purity , and perhaps point out which genes should be investigated as the next breast cancer drug targets," Professor Gregory Hannon

Video about the Cold Spring Harbor Laboratory 

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dos Santos, C., Rebbeck, C., Rozhkova, E., Valentine, A., Samuels, A., Kadiri, L., Osten, P., Harris, E., Uren, P., Smith, A., & Hannon, G. (2013). Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1303919110

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