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
New Treatment Cuts “Bad” Cholesterol in Half for a Full Year
A single infusion of an experimental CRISPR-Cas9 therapy was reported to safely lower LDL cholesterol by 52.5% and triglycerides by 47.8%, as measured 12 months after treatment. What if one infusion could keep cholesterol [...]
Too Much RNA Can Drain a Cell’s Energy, Scientists Discover
A virus may cripple a cell’s power supply simply by producing too much of a molecule the cell needs to survive. New research from the Texas A&M College of Veterinary Medicine and Biomedical Sciences [...]
West African scientists warn of weakening health systems and urge stronger outbreak detection
LOME, Togo (AP) — West African laboratory scientists called on governments Friday to strengthen capacity to detect disease outbreaks to avoid another major outbreak, saying health systems across the region are becoming weaker. Participants [...]
A Little-Known Protein Could Point to a New Way To Treat Alzheimer’s
A study suggests that increasing SORLA protein levels could help treat Alzheimer’s disease and other disorders involving tau protein. Increasing SORLA, a protein with a protective role in the brain, helped mice withstand damage [...]
Cancer’s Hidden Antioxidant Shield Helps It Escape the Immune System
Blocking an antioxidant protein that tumors use to suppress immune attacks improved cancer immunotherapy responses in mice. Cancer cells can release antioxidants that interfere with the immune cells trying to kill them. Researchers have [...]
Scientists Find a Berry Compound That Helps Muscle Cells Burn Fat
Pterostilbene, a compound found naturally in some foods, affects how skeletal muscles process fats by stabilizing a protein called PPARδ and increasing its signaling activity. Pterostilbene, a natural compound found in blueberries, grapes, and [...]
Two Hidden Forces Help Build the Human Brain Before Birth
Scientists have uncovered two surprising forces that help guide how the human brain forms before birth. Before birth, the human brain is shaped in large part by an unusual class of stem cells known [...]
Researchers Uncover a Hidden Trigger Behind Chronic Inflammation
The findings offer new insights that could help guide the development of future therapies. A protein called human resistin may help flip on one of the immune system’s most powerful inflammatory switches. Researchers at [...]
Scientists Have Uncovered Previously Hidden Microbial Activity on Human Skin
The most abundant microbes on your skin may not be the ones doing most of the work. Human skin supports vast communities of bacteria, fungi, and viruses that can influence its protective barrier, immune [...]
Brazilian Tree Compounds Fight COVID-19 on Multiple Fronts
Scientists found compounds in a Brazilian tree that hit SARS-CoV-2 on multiple fronts, revealing a promising new lead in the search for COVID-19 treatments. Researchers have found that galloylquinic acids extracted from the leaves [...]
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
New injectable treatment helps the brain rebuild after stroke
Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke. In experiments with mice, the material transformed the cavity created [...]
