Molecular circuit uncovered governing key cell-fate decisions
Critical missing links in a signaling-transcription cascade responsible for pivotal cell-fate decisions have been described for the first time in a paper in Cell.
Critical missing links in a signaling-transcription cascade responsible for pivotal cell-fate decisions have been described for the first time in a paper in Cell. Identified through a combination of simulations and experiments, the links are part of circuit-like molecular control mechanisms for converting analog signals into binary responses central to the development of all cells.
The question of how identical cells develop into distinct cell types using the same signaling pathways is integral to our understanding of the cell life cycle. The mechanisms that determine cell fate decisions, leading cells with the same genes to distinct developmental outcomes, remain however poorly understood.
To study cell fate decisions, a research team headed by scientists at the RIKEN Research Center for Allergy and Immunology (RCAI) and the University College Dublin administered growth factors to MCF-7 breast cancer cells and analyzed responses in the extracellular regulated kinase 1/2 (ERK) cascade. Whereas one growth factor (epidermal growth factor or EGF) induces transient ERK activity leading to cell proliferation, the other (heregulin or HRG) induces ERK activity that is sustained, triggering cell differentiation. Connecting these analog ERK signaling patterns to their cell fates (proliferation/differentiation) is the phosphorylated transcription factor c-Fos, whose digital all-or-none expression acts as the output of the signaling system.
Comparing observational data with results of mathematical simulations, the researchers arrived at a “molecular circuit” model for c-Fos mediated cell differentiation composed of negative feedback loops, feed-forward loops and logical AND gates that reduce noise and generate stable output signals. The discovery of these simple circuit components, which are believed to govern differentiation across a variety of different cell types, provides fundamental insights into the underlying logic of cell-fate decision processes, opening the door to applications in areas such as regenerative medicine.
For more information, please contact:
Dr. Mariko Okada-Hatakeyama
Laboratory for Cellular Systems Modeling
RIKEN Research Center for Allergy and Immunology (RCAI)
Tel: +81-(0)45-503-9104 / Fax: +81-(0)45-503-9613
Ms. Tomoko Ikawa (PI officer)
Global Relations Office
Tel: +81-(0)48-462-1225 / Fax: +81-(0)48-462-4715
gro-pr | Research asia research news
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
New technique promises tunable laser devices
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...