While the ability of human embryonic stem cells (hESCs) to become any type of mature cell, from neuron to heart to skin and bone, is indisputably crucial to human development, no less important is the mechanism needed to maintain hESCs in their pluripotent state until such change is required.
In a paper published in this week's Online Early Edition of PNAS, researchers from the University of California, San Diego School of Medicine identify a key gene receptor and signaling pathway essential to doing just that – maintaining hESCs in an undifferentiated state.
The finding sheds new light upon the fundamental biology of hESCs – with their huge potential as a diverse therapeutic tool – but also suggests a new target for attacking cancer stem cells, which likely rely upon the same receptor and pathway to help spur their rampant, unwanted growth.
The research, led by principal investigator Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, focuses upon the role of the highly conserved WNT signaling pathway, a large family of genes long recognized as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7.
"WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state," said Willert. "If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state."
The researchers proved this by using an antibody-like protein that binds to FZD7, hindering its function. "Once FZD7 function is blocked with this FZD7-specific compound, hESCs are no longer able to receive the WNT signal essential to maintaining their undifferentiated state."
FZD7 is a so-called "onco-fetal protein," expressed only during embryonic development and by certain human tumors. Other studies have suggested that FZD7 may be a marker for cancer stem cells and play an important role in promoting tumor growth. If so, said Willert, disrupting FZD7 function in cancer cells is likely to interfere with their development and growth just as it does in hESCs.
Willert and colleagues, including co-author Dennis Carson, MD, of the Sanford Consortium for Regenerative Medicine and professor emeritus at UC San Diego, plan to further test their FZD7-blocking compound as a potential cancer treatment.
Co-authors include Ian J. Huggins, Luca Perna and David Brafman, Department of Cellular and Molecular Medicine, UCSD; Desheng Lu and Shiyin Yao, UC San Diego Moores Cancer Center; and Terry Gaasterland, Scripps Institution of Oceanography and Institute for Genomic Medicine, UCSD.
Funding support for this research came, in part, from the California Institute for Regenerative Medicine and the UC San Diego Stem Cell Program.
Scott LaFee | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences