Of non-existent black holes and pickled stem cells
Posted by Kif Liakath-Ali, on 2 February 2014
Physics and Biology were the media darlings last week. Earlier, one of my favorite physicists Professor Stephen Hawking claimed through his paper that there are no black holes! Well… later I realized he actually insist in calling it with different name, “Metastable bound states of the gravitational field”!!! I know I am not meant to explore the nature of black holes. Nevertheless, While I was contemplating over the yes-or-no event horizon, there came hey-remember-you-are-a-biologist kind of reminder articles in Nature and makes a sensation. I first read about it from a random free newspaper on London Tube. Now you know how quickly it hit the media!
By now, most of people who work in the research field which uses key word “stem cells” should be aware of these two articles. So me not going into much details. Apparently, Haruko Obokata and Charles Vacanti’s team has done amazing job in showing a new method to derive iPS-like cells (as Yamanaka calls it). The method involves exposing the cells to stress, like comfortable acidic pH. And the rest of the story is well known.
Now, the lesson for me from these two articles is not only how I can reprogram cells in a new way but also how an alternative thinking can lead to breakthrough discoveries. Most of the scientists often plunged into narrow topics that often restricts to think outside the lab. As the lead author says, the original idea occurred to her when she thought about plants how they regenerate missing parts when it get chopped off. Obviously plants do not need to overexpress Yamanaka factors-like factors or any genetic manipulation to regenerate. In plants, mostly the regeneration is induced by stress. By inspired by this, the authors tried various stress applications including to squeeze the cells through narrow capillary pipettes (of course, without killing) and see if it could make the cells to do something different. And the ingenious idea of dipping cells in low pH worked out! Inspirations all around us, we need to keep eyes open, a bit wider.
Lateral thinking is vital in biology and science in general, I say!
This post is also available in our lab blog – wattlab blog. Please visit for more interesting topics and discussions.
Further reading
S. W. Hawking (2014) Information Preservation and Weather Forecasting for Black Holes. Preprint at http://arxiv.org/abs/1401.5761.
Obokata et al., (2014) Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature. 505, 641–647.
Obokata et al., (2014) Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature. 505, 676–680.
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Indeed Haruko Obokata and Charles Vacanti’s team data look amazing and even intriguing.
However one can wonder about the true mechanism of cell reprogramation that they report.
A decrease in extracellular pH does not affect so much intracellular pH and even less intranuclear pH. let’s recall that a cell has a lot of defense to withstand acidosis or alcalosis : a Na/H antiport a Na-dependent and a Na-independent Cl/HCO3 as well as intracellular proteins that buffers H+. a Ca2+/H+ mitochondrial exchanger. The nucleus has a K+/H+ exchanger pretty efficient to regulate intranuclear pH as well as chromatin that buffers a lot H+ . The reader of that paper would have like (love) to see in this paper which intranuclear pH is required to repress in a specific manner somatic genes and turn on embryonic genes in a similar specific manner. Can H+ feature such a specific effect on gene repression and transcrition?
How sure are the authors that their CD45+ faxed cells do not include some stem cells? Why doe it not work on adult somatic cell?
Can they reprogram a single clonal cell? This is what one can expect looking at the very high efficiency of their reprogramation protocol.
What was the virus load (maybe even acidifying the host cells) imposed to the cells when cells were reprogrammed with retroviral vectors and Yamanaka factors? a cell stress?
Let’s first see how many labs can reprogram somatic cells using their protocol
Any data specifically in the stem cell field needs to be challenged. The hope of patients about regenerative medecine is so high that scientists have to be very cautious before releasing scientific data in the news
Thanks for sharing your thoughts Michel. It is appreciated. You are right from cell physiology perspective. I think the emerging stem cells energetics area could tackle these questions.
We too discussed similar questions as yours. It could be that the pluripotency pathways may be induced even with a subtle change in extracellular pH without altering the cytoplasmic homeostasis itself. And we know that the stem cell milieu/niche have greater impact on the cell state by acting via receptors.
Obviously, there will always be challenges about reproducibility of any data published. And we will know in couple of years if not more, how this method is. My motive for writing about these articles is primarily to highlight the need of creative thinking in Science.