Stem cell stories that caught our eye: Zika virus and brain stem cells, new guidelines, re-growing tails and better iPS cells

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Three more studies on Zika and brain stem cells. It’s heartening to see how quickly the scientific community has reacted to the recent Zika virus epidemic. They have already completed and published dozens of research projects. And science journals have responded by not only speeding up their often slow process to get results published, but also some are removing pay walls to ease disseminating the data.

After a pair of studies earlier this month showed how the virus could impact brain stem cells in mini human brain “organoids” in the lab, three studies this week showed how the virus does its damage in animal models. A colleague wrote two blog posts on the human mini-brain studies, one revealing the entry point the virus uses to enter brain stem cells and the other finding the virus negatively impacts the ability of brain stem cells to specialize into mature brain.

 

Zika in placenta Wash U

Zika virus (red) in a mouse placenta (Washington U.)

While those organoids can tell us a lot, they don’t show what happened when the fetus matures, so the new mouse models provided the first conclusive link between infection and microcephaly—the small brains seen in children born following their mother’s infection with the virus. But the three studies muddied the water a bit on the cause of the reduced brain size. One suggested that damage to the placenta could have reduced blood flow to the developing fetus. The other studies showed that the virus does indeed infect brain stem cells, but one suggested that the bulk of the damage from the virus occurs later in pregnancy acting directly on mature nerve cells, not the stem cells.

The papers in Cell from Washington University in St. Louis, in Nature, from the University of California, San Diego and in Cell Stem Cell from the Chinese Academy of Science got wide media coverage. Genetic Engineering News and Science Magazine did some of the most thorough reporting and Newsweek wrote a piece a bit easier to understand.

 

Stem cell research guidelines.  When an august scientific body issues guidelines for its work, the public generally either ignores it or never hears about it. That paradigm shifted a bit this week when the International Society for Stem Cell Research issued revised guidelines for numerous aspects of regenerative medicine research and practice. A large part of the difference probably resulted from the group self-cautioning its members to avoid hype and not oversell their results.

The Bloomberg business wire issued a story with the headline, “Stop Hyping Stem Cell Science, Say Stem Cell Scientists.” Four scientific journals simultaneously published various reviews of the guidelines including one in Science authored by five members of the 25-person committee that drafted them. That piece carried the title, “Confronting Stem Cell Hype.”

One of the authors, Tim Caulfield of the University of Alberta, acknowledged changing the discourse in the field will not be easy:

 “Because the forces that twist how science is communicated are complex, systemic, and interrelated, correcting for science hype will not be easy.”

Beyond the hype, the guidelines address several important issues in our field calling for:

  • a process to review all embryo research, not just when the embryo is destined to be a source of stem cells;
  • support for laboratory research on genetically modifying sperm, eggs and embryos, but banning such techniques for clinical use at this time;
  • defining proper research and clinical use of techniques to swap out healthy mitochondria, for defective ones in cells;
  • allowing compensation for women who donate eggs for research within certain defined parameters
  • creating robust standards for evaluating the outcome of stem cell clinical trials.

 

Just a few switches to regrow a tail.  Many lizards and amphibians regrow their tails with ease, but prior research has shown a great many genes get turned on to make it happen. Now, a team at Arizona State University has shown that just three genetic switches orchestrate much of that gene activity.

arizona_green anole lizard

Green Anole lizard (Arizona State U.)

The tiny genetic components called microRNAs turn out to be very powerful on-off switches for genes and can control many different genes at the same time.

 “Since microRNAs are able to control a large number of genes at the same time, like an orchestra conductor leading the musicians, we hypothesized that they had to play a role in regeneration,” said senior author Kenro Kusumi in a story in Bioscience Technology.

 The group hopes their research will lead to ways to get tissue regeneration in humans for repairing damage such as spinal cord injury or worn knee cartilage.

 

Making better iPS cells.  Although we have known for a decade the basics of how to turn an adult cell into an embryonic-like stem cell, iPS cells, virtually that entire time researchers have sought ways to make them even more like embryonic stem cells. Too often iPS cells retain memory of the adult cell they came from and stubbornly refuse to turn into certain other types of tissue.

Researchers at the University of Pennsylvania have shed light on this stubborness using an emerging field called “3D epigenetics.”  Epigenetics looks at the various controls that turn genes on and off, but it traditionally cannot take into account the effect of DNA folding that puts genes next to each other adding a layer of regulation based on juxtaposition.  They found that in some iPS cells the DNA folding looked more like mature cells than embryonic stem cells, but that by manipulating the way the cells were grown they could modify that folding.

 “Our observations are important because they suggest that, if we can push the 3-D genome conformation of cells that we are turning into iPS cells to be closer to that of embryonic stem cells, then we can possibly generate iPS cells that match gold-standard pluripotent stem cells more rapidly and efficiently,” said graduate student Jonathan Beagan in a university press release.

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