Altering a cellular process can lead stem cells—cells from which other cells in the body develop—to die or regenerate, according to a new study led by Cedars-Sinai and the University of California, San Francisco (UCSF).
The findings, to be published today (January 13) in the peer-reviewed journal Cell Stem Cell, may assist in the development of new drugs that can manipulate this process to slow or stop cancer from growing and spreading, and enable regeneration in the context of other diseases.
Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s and the senior author of the study, said the findings underscore the body’s need to produce just the right amount of new cells.
The body’s cells are regulated by various biological pathways. Each pathway involves a series of molecular actions inside a cell that produce a change in the cell, like creating a new molecule, such as a protein.
For this study, investigators at Cedars-Sinai and UCSF observed the effects of a gene called Discs large 1 (Dlg1) on the Wnt signaling pathway. This pathway involves a series of molecular interactions that regulate the growth or death of stem cells.
The Wnt pathway, which begins on the surface of a cell and ends inside of it, is critical for stem cell renewal and tissue regeneration. Although the pathway has been studied extensively, much is still unknown about how small increases and decreases in the frequency of communication signals through the pathway may affect the creation of new cells.
“The signals or instructions can vary over time and under different conditions of health and disease,” said Klein, the David and Meredith Kaplan Distinguished Chair in Children’s Health.
Investigators studied intestinal tissue samples from laboratory mice to learn how mutations in Dlg1 affect the interaction between Wnt signaling and stem cells in the highly regenerative gastrointestinal tract. By performing gene expression analysis on the samples, the team looked for changes in genes that typically send signals along the Wnt pathway.
Through this process, investigators were able to see how changes in signaling frequency affected the creation of stem cells. The investigators found that when they inhibited the expression of Dlg1 and then increased signaling along the Wnt pathway by the addition of a specific molecule, such as a virus or drug, the stem cells died rather than generate new daughter cells.
“By better understanding cell signaling, we can learn how to use a molecule to speed up or slow down this pathway and normalize signaling so that a given organ has the right number of cells,” said David Castillo-Azofeifa, PhD, co-first author of the study and now a principal scientist at Genentech, Inc. Castillo-Azofeifa was a postdoctoral fellow in Klein’s laboratory at UCSF.
“The proper interpretation of the levels of signaling is critical for the stem cells’ survival,” said Tomas Wald, PhD, the other co-first author of the study and a scientist in Klein’s laboratory.
Investigators next plan to study the Wnt pathway and the role of Dlg1 in samples taken from human intestines to see if they replicate what was observed in laboratory mice.
In a new study, scientists with the University of Florida have found that a combination of silver nanoparticles and antibiotics is effective against antibiotic-resistant bacteria. The researchers hope to turn this discovery into viable [...]
Peritoneal cancer is difficult to treat and has a poor survival prognosis. But a new and effective nanomedicine delivery system is offering some hope. The company is called NaDeNo and is well underway with [...]
According to a new study by researchers at Penn Medicine, ketamine, which is well-known as an anesthetic and is becoming increasingly popular as an antidepressant, dramatically reorganizes activity in the brain, almost as if [...]
A new immunotherapy releases cancer-killing cytokines only within the tumor. Researchers at the University of California San Francisco (UCSF) have developed a new T cell-based immunotherapy that selectively targets cancer cells, producing a powerful anti-cancer cytokine [...]
An AI was tasked with creating proteins with anti-microbial properties. Researchers then created a subset of the proteins and found some did the job. An AI has designed anti-microbial proteins that were then tested [...]
Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right [...]
By one unique metric, we could approach technological singularity by the end of this decade, if not sooner. A translation company developed a metric, Time to Edit (TTE), to calculate the time it takes for professional [...]
Phase transition in early universe changes strength of interaction between dark and normal matter. Dark matter remains one of the greatest mysteries of modern physics. It is clear that it must exist, because without [...]
Summary: Researchers have developed a new family of nano-scale capsules capable of carrying CRISPR gene editing tools to different organs of the body before harmlessly dissolving. The capsules were able to enter the brains of [...]
An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a study led by investigators at Weill Cornell Medicine. The [...]
Using a mouse model, Japanese researchers unleash the likely mechanism of action of Actinidia arguta (sarunashi) juice on lung cancer development. Lung cancer is a leading cause of death in Japan and across the [...]
When used as wearable medical devices, stretchy, flexible gas sensors can identify health conditions or issues by detecting oxygen or carbon dioxide levels in the breath or sweat. They also are useful for monitoring [...]
Novel drugs, such as vaccines against covid-19, among others, are based on drug transport using nanoparticles. Whether this drug transport is negatively influenced by an accumulation of blood proteins on the nanoparticle’s surface was [...]
The costly lesson from COVID: why elimination should be the default global strategy for future pandemics
Imagine it is 2030. Doctors in a regional hospital in country X note an expanding cluster of individuals with severe respiratory disease. Rapid whole-genome sequencing identifies the disease-causing agent as a novel coronavirus. Epidemiological [...]
A predictive model has been developed that enables researchers to encode instructions for cells to execute. Scientists at the University of California, San Francisco (UCSF) and IBM Research have created a virtual library of thousands of “command sentences” [...]
It's "lights out" for antibiotic-resistant superbugs as next-generation light-activated nanotech proves it can eradicate some of the most notorious and potentially deadly bacteria in the world. Developed by the University of South Australia and [...]