Tag Archives: stem cells

The 2012 Nobel Prize in Physiology or Medicine

Yesterday, the Nobel committee in Stockholm announced that the 2012 Prize in Physiology or Medicine would be going to John B. Gurdon and Shinya Yamanaka for the discovery that adult, differentiated cells could be de-differentiated again into pluripotent cells.

In countries where research on embryonic stem cells is essentially frozen — like Japan, for instance — this variety of pluripotent cells could prove to be a boon. More importantly, experiments done by these men revolutionized our understanding of the cellular lifecycle; no longer was it unidirectional, where cells moved down a one-way path into specialization.

I especially liked SciAm’s profile of Yamanaka’s work. His research showed that a bare handful of genes — four, to be precise — could turn back cellular time and ‘regress’ the cell into its pluripotent state.

…[Yamanaka]uncovered 24 factors that, when added to ordinary mouse fibroblast cells and subjected to the correct culturing procedures, could create pluripotent cells virtually identical to stem cells. Yamanaka kept examining each factor and found that none could do the job alone; instead a combination of four particular genes did the trick.

Note the “virtually identical” in that paragraph.

Yamanaka and others do not think that iPS cells can replace their embryonic counterparts yet. “We don’t yet know if embryonic stem cells and iPS cells are truly equivalent,” says Konrad Hochedlinger of Massachusetts General Hospital’s Center for Regenerative Medicine.

There are other issues with pluripotent cells: they need to be injected with some kind of retrovirus, which would leave the new cells full of the potential to attack our immune system. They’ve been working on this, however, and now Yamanaka’s team has come up with a way to use a circular, double stranded round of DNA called plasmids to replace retroviruses.

Yamanaka’s lab reported success using plasmids, or circular pieces of DNA. Other retrovirus alternatives include proteins and lipid molecules.

The risks don’t end there. Since one of the genes that controls the induction of pluripotency is strongly cancerous, there’s a chance that the stem cells could become tumorous too. There’s still hope, though:

…the transcription factor c-Myc happens to be a powerful cancer gene, and the cells produced by Yamanaka’s team tended to become cancerous. “Making iPS cells is very similar to making cancer,” he explains. In principle, c-Myc may not be necessary: in mice, Yamanaka and a group led by Rudolf Jaenisch at the Massachusetts Institute of Technology found a way to avoid using c-Myc, in part, by optimizing culture conditions.

 

 

Advertisements

Daily Roundup: Living Longer, Better

A little break from the mechanics of the last few posts: yesterday’s news consisted of some startling, and possibly controversial, biological revelations.

It’s been known for a while now that women outlive men, by about five to six years. Looking through some simple statistics, it’s clear that this has been the case as early as 1930, so better living conditions for women and improved access to female healthcare might not tell the whole story. Some scientists in Lancaster University think they have the answer: mitochondrial genetic inheritance.

Mitochondria are tiny organelles believed to have been co-opted by eukaryotic organisms (which includes humans) a couple of billion years ago. Eukaryotic organisms — my high-school biology is slowly returning to me! — are creatures whose internal structures are enclosed and separated by membranes. Most important of these internal structures is the nucleus; prokaryotes lack one, and eukaryotes are defined by it.

Mitochondria are one of the most important of these internal structures. Producers of ATP, the cell’s energy source, they are crucial to cellular health. One of the reasons that mitochondria are theorized to be symbiotic with our bodies is that they actually contain their own version of DNA, with a handful of genes that code for proteins important to respiratory processes, or the production of energy via ATP. The idea of a mitochondrial Eve arose when biologists discovered that every child carries only the mother’s copy of the mitochondrial DNA. There’s no recombination analogous to the meeting of egg and sperm; the entire DNA of the mitochondria is simply handed down from mother to child1.

Scientists from Lancaster conducted a rather interesting study to figure out if this mitochondrial handing-down had any effects on the males as opposed to the females. Using some fruitflies, they determined that variations in mitochondrial DNA seemed to correlate with male life expectancy, while they had no effect on female life expectancy. The idea, if I understand it correctly, is that mutations that are harmful for women don’t accumulate, since natural selection weeds out the women who couldn’t have survived nearly as well. But they may very well have preserved mutations harmful to men. This could mean that the mutations which contribute, in whatever small way, to a smaller male lifespan, would be passed on through generations. The Lancaster researchers argue that the “Mother’s Curse”, which is probably the most frustratingly hyperbolic scientific contraction I’ve heard, would account for reduced male life expectancies.

It’s an interesting hypothesis, but I think I’ll wait for the experiments to be either repeated or something analogous to be discovered in human research. It’s rather too sweeping a realization, especially when combined with the assertion that this could have implications across all species that have similar life expectancy gaps. Does the mitochondrial inheritance work the same way across all of them? If not, what other factors could contribute? This rather well-annotated Wikipedia article indicates that mitochondrial DNA is remarkably slow in accumulating mutations — perhaps once every 3500 years, or 35 human generations. That’s plenty of time to develop mutations harmful to men, but it would be interesting to see where the life expectancy differences began to show up, corresponding to the mutations in DNA.

Another article, this one far more controversial, was the link between persistent cancer and something called “cancer stem cells”. Researchers in three different studies tracked pre-cancerous tumors and found that most of the cell populations in later stages of division had descended from a small subset of the original cell population. In the study conducted by researchers from Belgium, it was reported that the cancer stem cells looked similar to skin stem cells.

At first, the idea of cancerous stem cells seemed rather paradoxical to me. After all, cancer is the result of a small population of cells gone wild, refusing to undergo apoptosis where they trigger a sort of self-destruct mode. But this must begin in some fairly mature, developed, specialized cells of internal organs.  So I’d like to discover how cancerous cells grow and spread across the body, causing the cells of other internal organs to go rogue.

It might be time to do more research — and talk to a graduate student I know…

Footnote:

1.  A whole other interesting tangent is the idea of the “mitochondrial Eve”, the ancestor of most living humans today whose genetic inheritance can be traced in an unbroken line to today’s women. This Wikipedia article gives a little bit of an overview, although more citations are probably needed.