Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Researchers find a novel way to tease out key factor involved in heart muscle maturation

Researchers find a novel way to tease out key factor involved in heart muscle maturation

Scientists around the world have been trying to replace damaged heart tissue using lab-made heart-muscle cells (cardiomyocytes), either injecting them into the heart or applying patches laced with the cells. But results to date have been underwhelming.

“If you make cardiomyocytes in a dish from pluripotent stem cells, they will engraft in the heart and form muscle,” says William Pu, MD, director of Basic and Translational Cardiovascular Research at Boston Children’s Hospital. “But the muscle doesn’t work very well because the myocytes are stuck in an immature stage.”

How the cardiomyocytes that we start developing before birth become vigorously contracting adult heart muscle cells hasn’t been well understood.

“I think there are specific signaling pathways that control that process, which we haven’t been able to reproduce in a dish,” says Pu.

Selective deletions

Studying cardiomyocyte maturation in live mice has been equally challenging. Prior studies have tried genetically engineering mice with different genes “knocked out” in their heart muscle to figure out which ones are required. But complete loss of a gene often causes dysfunction of the entire heart, which itself can impair maturation. Moreover, breeding multiple strains of “knockout” mice with different genes deleted is an expensive, time-consuming procedure.

In a new study published September 21 in Nature Communications, Pu and colleagues bypassed these hurdles. Using live mice and CRISPR/Cas9 gene editing technology, they teased out a key factor involved in heart muscle maturation in a new and novel way.

The beauty of their approach is two-fold. First, it required just one mouse strain that expresses the Cas9 enzyme, coupled with a virus that directs Cas9 to delete a specific gene. To target different genes, the researchers simply made small modifications to the virus.

“We were able to test 10 potential genes of interest within 10 weeks,” says Pu.

Second, rather than delete the gene in every cell, the researchers injected the virus such that roughly 1 in every 10 heart muscle cells was affected. This “mosaic” delivery pattern allowed the unaffected heart muscle to keep functioning. The team could then study the mutated heart muscle cells separately.

Regulating heart muscle development

One factor, known as serum response factor (SRF), emerged as a key regulator of cardiomyocyte maturation. When the Srf gene was deleted in the heart muscle of newborn mice in a mosaic fashion, many aspects of maturation were disrupted.

In normal, mature myocytes, the basic contractile structures, known as sarcomeres, are highly organized. But in the mutant myocytes, the sarcomeres became disorganized. Furthermore, normal cells develop transverse tubules, important structures that help to coordinate sarcomere contraction. These too were greatly disrupted in the mutant myocytes. Finally, the mitochondria, which provide energy and are normally arrayed alongside the sarcomeres in brick-like fashion, were dramatically reduced in size and number.

In further experiments, the team showed that SRF regulates the activity of multiple other genes, including critical sarcomere genes, in immature cardiomyocytes, but not in mature cardiomyocytes. They think that SRF receives signals from the rest of the cell which cue it to execute a master organization program during maturation.

Finally, Pu and colleagues showed that sarcomeres themselves must be properly assembled for other aspects of maturation to occur. “We learned that sarcomeres are not just important for contraction, but are probably driving the maturation program,” says Pu.

Making heart cells grow up

Overall, the results would seem to suggest that if you could just find a way to boost SRF, you could get lab-made heart muscle cells to grow up. But it wasn’t that simple: When SRF was over-expressed, the cells looked the same as those without SRF at all.

And that sets up the lab’s next goal.

“Cells seem very sensitive to the level of SRF,” says Pu. “You probably can’t manipulate SRF itself. You have to understand what’s controlling it upstream.”

Source:

https://www.childrenscolorado.org/

Tagged with:

About author

Related Articles