Blood cells have limited lifespans, which means that they must be continually replaced by calling up reserves, and turning these into the blood cell types needed by the body. Claus Nerlov and his colleagues at the European Molecular Biology Laboratory (EMBL) unit in Monterotondo, Italy, in collaboration with researchers from Sten Eirik Jacobsen’s laboratory at the University of Lund in Sweden, have now uncovered how an intracellular communication pathway contributes to this process. Because defects in such pathways and in the development of stem cells frequently lead to leukemia and other diseases, the work should give researchers a new handle on processes within cells that lead to cancer. The work is published in this week’s online issue of Nature Immunology.
Over the past decades, molecular biologists have identified several pathways – sequences of molecules which manage the flow of information within the cell – responsible for major biological processes. One of these, the “Wingless” pathway, plays a vital role in shaping tissues and organs in developing embryos of nearly all animal species. It also helps organisms manage stem cells, by keeping them on hold and preventing their differentiation until the right time. Such pathways are usually switched on and off by external stimuli that help cells respond properly to the environment. Now Peggy Kirstetter and other members of Nerlov’s lab have shown what happens when Wingless is too active in hematopoietic stem cells in mice.
“We modified one element of the pathway, a protein called beta-catenin, so that it was stuck in ‘transmission mode,’” Kirstetter says. “This created cells in which the pathway was always switched on. We’ve known that Wingless contributes to blood differentiation, but didn’t know how the signals were being transmitted within the hematopoietic stem cell.”
The modified protein had dramatic effects. Usually, most cells undergo numerous transitional stages on their way from stem cells to fully-developed types in the blood. Several types of blood cells vanished entirely; the same thing happened to more basic cell types higher up in the blood lineage hierarchy. Particular kinds of stem cells disappeared from the bone marrow of the mice. Others were too frequent. Bone marrow cells didn’t develop into myeloid and red blood cells. B- and T-cells were also blocked at early stages, but in a different way. This hints that they may be controlled by other protein links in the Wingless pathway as well. Perhaps most strikingly, beta-catenin appears to make cells take decisions about their fate before they leave the stem cell compartment in the bone marrow, something so far not thought to occur.
The study proves that beta-catenin plays a central role in determining whether blood cells form or not. On the other hand, an overactive Wingless pathway doesn’t seem to damage cells that already exist. Thus beta-catenin seems to be a decision-maker, a selector of how information gets routed within the cell, rather than something which maintains the vitality of existing cells.
Nerlov compares the breakdown to people standing at a fork in a labyrinth, hesitating before they go on. “We know there are strong connections to cells’ decisions to divide, to develop or to die. If cells don’t commit themselves to the right developmental path at the right time, they’re very likely to die or to begin an inappropriate type of reproduction. Acute leukemias and other forms of cancer cells derive from defects such as this. Understanding the processes by which they form will require pinpointing the forks in the road where things go wrong.”
Anna-Lynn Wegener | alfa
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences