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.
News
Ethics in Nanomedicine: Key Issues and Principles
Nanomedicine, a branch of nanotechnology, is revolutionizing healthcare by enabling the manipulation of materials at the nanoscale to diagnose, treat, and prevent diseases. Unlike traditional treatments, nanoparticles (NPs) are highly precise in targeting diseased [...]
A call for robust H5N1 influenza preparedness and response
As the global threat of H5N1 influenza looms with outbreaks across species and continents including the U.S., three international vaccine and public health experts say it is time to fully resource and support a [...]
Mucosal COVID-19 boosters outperform mRNA shots in preventing upper airway infections
In a recent study published in Nature Immunology, a team of researchers from the United States used non-human primate models to compare the protection conferred by an intramuscular booster dose of the bivalent messenger ribonucleic acid [...]
How Space Travel Really Changes Astronauts – From the Inside Out
International team reveals previously unknown effects on physiology that could shape the future of long-duration space missions. Researchers have discovered significant changes in the gut microbiome due to spaceflight, which affects host physiology and [...]
Breakthrough in blood stem cell development offers hope for leukemia and bone marrow failure
Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalized treatments for children with leukemia [...]
Scientists Develop Game-Changing Needle-Free COVID-19 Intranasal Vaccine
A new mucosal COVID-19 vaccine poised to revolutionize the delivery process is especially beneficial for those with a fear of needles. A next-generation COVID-19 mucosal vaccine is set to be a game-changer not only when delivering [...]
Scientists Develop All-in-One Solution To Catch and Destroy “Forever Chemicals”
A new water treatment system developed by UBC researchers efficiently removes and destroys PFAS pollutants using a dual-action catalyst, offering a sustainable and cost-effective solution for water purification challenges. Chemical engineers at the University of [...]
New method accelerates drug discovery from years to months
Researchers from the University of Cincinnati College of Medicine and Cincinnati Children's Hospital have found a new method to increase both speed and success rates in drug discovery. The study, published Aug. 30 in [...]
A new smart mask analyzes your breath to monitor your health
Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health. [...]
Study reveals the role of blood clotting in COVID-19
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks [...]
A Novel Cancer Vaccine Combining Nano-11 and ADU-S100
In a recent article published in npj Vaccines, researchers detailed the development of a novel cancer vaccine that combines a plant-derived nanoparticle adjuvant, Nano-11, with a clinically tested STING agonist, ADU-S100. The primary objective was [...]
AI spots cancer and viral infections with nanoscale precision
Researchers have developed an artificial intelligence which can differentiate cancer cells from normal cells, as well as detect the very early stages of viral infection inside cells. The findings, published today in a study [...]
Tiny shards of plastic are increasingly infiltrating our brains, study says
Human brain samples collected at autopsy in early 2024 contained more tiny shards of plastic than samples collected eight years prior, according to a preprint posted online in May. A preprint is a study which has not yet [...]
Scientists Have Discovered Strange DNA in Our Brains – and It Could Be Shortening Our Lives
According to the research, these mitochondrial DNA insertions could be linked to early death. Mitochondria in brain cells frequently insert their DNA into the nucleus, potentially impacting lifespan, as those with more insertions were found to [...]
Watch Out After a Hospital Stay: You Could Be Exposing Your Family to Superbugs
Research indicates hospitals contribute to the local spread of antibiotic-resistant infections. A recent study published in the journal Infection Control & Hospital Epidemiology by the Society for Healthcare Epidemiology of America suggests that family members of [...]
Molecular Trickery: How COVID-19 Silently Sabotages the Human Immune System
Researchers have discovered that SARS-CoV-2 manipulates the human immune system by forcing cells to produce non-functional proteins, hindering the body’s antiviral defenses. This groundbreaking study by teams from prestigious Brazilian universities highlights potential targets for new COVID-19 treatments, [...]