If you’ve stayed current with the STAP cell fiasco you know it’s been a wild ride.
STAP cells, or Stimulus-Triggered Acquisition of Pluripotency cells, caught the imagination of many in late January through their sheer simplicity: You hit cells with a shock of acidic conditions, and they become pluripotent. That’s it. No Yamanaka factors required.
The media oddly dubbed STAP cells “acid-bath” stem cells.
Fast forward several months and we have calls for retractions of the original paper, allegations of research misconduct in the matter, and implication that Haruko Obokata, the 30-year old researcher at Riken (who still maintains that STAP cells exist), has been thrown under the bus by her scientific mentors.
But despite the strange story arc STAP cells have taken, I believed that some aspects of the STAP cell ideas would eventually be accepted as useful results. I thought that the claims would end up tempered with a subsequent paper. So too, did a Riken spokesperson, who managed to differentiate between cells expressing pluripotency markers, which STAP cells do, and cells acquiring a full-blown pluripotency phenotype, which we’re not so sure about anymore.
My own research has taken an arc from the stem cell field over to cancer research, where I happen to be researching mutational mechanisms that contribute to esophageal cancer.
It turns out that esophageal cancer is the end point on a spectrum of diseases. At the beginning, chronic acid reflux exposes the esophagus to the low pH levels of stomach acid, which is a risk factor for Barrett’s Esophagus. Barrett’s, in turn, is a risk factor for developing this type of cancer, which may take several decades to appear.
My original thoughts when STAP cells were first reported were that there would be a clear link between acidic conditions and stemness. Stomach acid is orders of magnitude more acidic than the 5.7 pH treatment required to produce STAP cells, which is similar to that of normal rain water, and therefore could possibly produce STAP cells in the esophagus.
But there’s no overwhelming evidence to suggest that that happens. One report in 2008 found Sox2 in cells that are precursors to Barrett’s Esophagus, and a more recent one claims to have observed Oct4 in Barrett’s itself. There’s even an argument that the disease comes from embryonic precursor cells that are freed from competition with other cell lineages. This model depends on the shutdown of another protein, p63, which as most readers here likely know is not a Yamanaka factor.
So from my perspective, it doesn’t look likely that STAP cells will help explain any mechanisms behind esophageal cancer, at least in my corner of work. I really wish that it would, as it would combine two of my interests and let me consider very interesting questions, but as the bright future of STAP cells recedes after every additional “gotcha” linked to the discovery-turned-hypothesis, it becomes clear that any work I could do would be based on little more than a handful of speculative ideas.
Chen X., Qin R., Liu B., Ma Y., Su Y., Yang C., Glickman J., Odze R. & Shaheen N. Multilayered epithelium in a rat model and human Barrett’s esophagus: similar expression patterns of transcription factors and differentiation markers, BMC Gastroentereology, 8 (1) DOI: doi:10.1186/1471-230X-8-1
Wang X., Yang S., Zhao X., Guo H., Ling X., Wang L., Fan C., Yu J. & Zhou S. (2014). OCT3 and SOX2 promote the transformation of Barrett’s esophagus to adenocarcinoma by regulating the formation of tumor stem cells., Oncology reports, PMID: 24481676
Wang X., Ouyang H., Yamamoto Y., Kumar P.A., Wei T.S., Dagher R., Vincent M., Lu X., Bellizzi A.M. & Ho K.Y. & Residual embryonic cells as precursors of a Barrett’s-like metaplasia., Cell, PMID: 21703447
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