But scientists in the lab of Whitehead Member Rudolf Jaenisch didn’t have to resort to these genetic markers in their latest experiment because the results were easy to see. Building on their widely publicized June Nature paper, which demonstrated that it’s possible to convert specialized mouse skin cells into unspecialized stem cells, Whitehead postdoctoral researchers Alexander Meissner and Marius Wernig have now identified successfully reprogrammed cells by looks alone.
Their findings, which appear online in the journal Nature Biotechnology on Aug. 27, bring human stem cell therapies a step closer to reality. Before reprogramming can be applied to our own species to generate custom embryonic stem cells, scientists must be able to accomplish it without altering the DNA of the cells involved.
“This eliminates one of the major hurdles to reprogramming human cells,” says Jaenisch, who is also an MIT professor of biology. “If we overcome the other obstacles, this approach could one day provide custom human embryonic stem cells for use in therapy.”
Last spring, Wernig and Meissner relied on genetic markers to identify successfully reprogrammed cells. This required them to work with fibroblasts from a genetically modified mouse. The mouse was grown from embryonic stem cells that contained foreign DNA coding for antibiotic resistance. The scientists had strategically inserted these foreign DNA “markers” at particular points along the genome, next to genes expressed only in embryonic stem cells. All of the cells (including fibroblasts) in the resulting mouse contained the markers.
In the original experiment, the researchers took fibroblasts from the tail of this mouse and infected them with a special virus containing four genes (Oct4, Sox2, c-myc, and Klf4) capable of converting the cells to an embryonic state. Genes typically active in embryonic stem cells roared to life, triggering the adjacent foreign DNA to provide antibiotic resistance. Thus only fully reprogrammed cells survived exposure to an antibiotic, which allowed the scientists to isolate them.
“When we conducted the original experiment, we noticed that many of the infected cells had already started to change shape before the markers were activated,” says Wernig.
So they set up a new experiment to test if visual identification alone would work. Indeed, they were able to separate the reprogrammed cells from ordinary fibroblasts under a microscope, based on several physical differences. Fibroblasts are big and flat. Embryonic stem cells are small, round and form tight colonies.
“We’ve shown that there’s no need to use markers to isolate successfully reprogrammed cells,” says Meissner. “This significantly simplifies this approach in mice, as we can now work with ordinary fibroblasts.”
But another hurdle remains before the technique can be applied to human cells.
“We still used viruses containing foreign DNA to introduce the genes that induced the reprogramming,” explains Meissner.
The scientists are now working to eliminate the virus from the reprogramming process. Jaenisch believes they will eventually succeed and points out that the technique could eventually yield a bountiful supply of custom human embryonic stem cells for use in therapy.
Meissner and Wernig successfully reprogrammed about 0.5 percent of the fibroblasts. Given that there are millions of cells in a typical skin biopsy (researchers used skin from either the end of the tail or from the ear of the mouse), that translates into thousands of stem cells, each one capable of developing into any cell type of the body.
Ceal Capistrano | EurekAlert!
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research