Our bodies are rife with disappearing potential. We come from stem cells, which can give rise to all the diverse types of cells in the human body. They can produce neurons, muscle cells, skin cells and more. As their daughters become more and more specialised, they lose this ability and become stuck with a specific fate. That’s the standard story – a one-way street of lost potential. The story is wrong. According to a provocative new study from Christine Chaffer at the Whitehead Institute for Biomedical Research, some specialised cells can spontaneously revert back to a stem-like state. The one-way street actually works two ways. It’s a very surprising result. Until now, no one thought that these reversions were possible, and scientists have spent a lot of effort finding ways of artificially reprogramming specialised cells into a stem-like state. Now it turns out that cells can naturally do the same thing. It’s like suddenly discovering that the people you pass every day in the street have been secretly gaining superpowers under your nose. All of this started with a simple observation. Chaffer was looking at a flask full of human breast cells and noticed that a small of them were floating, rather than stuck to the bottom. She says, "Normally when we see floating cells in tissue culture, they are dead or dying. However, in this case, I noticed that they maintained a healthy appearance." Chaffer was intrigued, especially since she knew that this ability to survive in a free-floating environment was a trait that stem cells share. "We suspected that these floating cells may contain a high proportion of a stem-like cell population," says Chaffer, and she was right. Compared to other breast cells, these floaters were more likely to show three genetic markers that are telltale signs of stem cells. These include a weakly active CD24 gene, a missing ESA gene and, most of all, a strongly active CD44 gene. These cells certainly behaved like stem cells. Even a single one could eventually produce clumps of breast gland tissue known as “mammospheres”, just like normal stem cells can. And when they were transplanted into mice, they could produce more complicated structures like milk ducts. These “stemmy” cells seemed to come out of nowhere. Chaffer found that groups of cells with weakly active copies of CD44 would quickly develop daughters that had the strongly active version of the gene. This wasn’t because of any contamination – the high-CD44 cells actually grow more slowly than their low-CD44 counterparts, so they would normally be drowned out in a bustling culture. It became clear that the low-CD44 cells were actually turning into the high-CD44 ones. This isn’t just something that happens in laboratory flask. Chaffer also found her special cells in fresh tissue samples, where they initially account for one in every 300 cells. Over time, other cells spontaneously turned into these stem-like ones.
This story would have been surprising enough, but Chaffer also found that breast cancer cells can turn into breast cancer stem cells. Cancer stem cells were discovered around 14 years ago, and they have since been found in many different types of tumour. The idea, and it’s still a controversial one, is that these elite cells produce most of the cancerous cells that make up a tumour. They could seed new tumours in different parts of the body, and regenerate tumours that have been mostly killed off by treatments, leading to recurrence. When Chaffer transformed the floating breast cells into cancer cells, she found that the low-CD44 ones could transform into high-CD44 cancer stem cells around 2-5 times more quickly than their normal cousins. And the resulting tumours were more aggressive than normal. This opens up a big can of worms. Several researchers are now trying to develop treatments that target cancer stem cells. The hope is that such drugs would seek and destroy the heart of tumours, robbing them of their ability to bounce back. But clearly, if normal breast cancer cells can turn into cancer stem cells, then this approach has a fatal flaw – the tumours could simply regenerate their heart. If that seems pessimistic, Chaffer’s discovery heralds more optimistic news in other fields of medicine. Many scientists are furiously working on ways of reprogramming adult cells into stem-like ones, often by altering the cells at a genetic level. The resulting cells could be used to produce new tissues or even organs, all tailored to an individual patient’s genome. There are risks to this approach, including (ironically enough) cancer, brought on by accidental changes to the wrong genes. But if Chaffer can work out how her cells were naturally regaining their “stemminess”, she could potentially find ways of duplicating the effect, without having to disrupt any genes. "If one can identify these particular population of cells in other tissues, they will hold great promise for the development of patient-specific adult stem cells for the treatment of degenerative diseases," she says. Reference: Chaffer, Brueckmann, Scheel, Kaestli, Wiggins, Rodrigues, Brooks, Reinhardt, Su, Polyak, Arendt, Kuperwasser, Bierie & Weinberg. 2011. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. PNAS http://dx.doi.org/10.1073/pnas.1102454108Image by the JCBDisclosure: In my day job, I work for a cancer charity called Cancer Research UK. The charity did not fund this study, but I have linked to its blog (which I occasionally write for) in a few instances above. More on stem cells: