Genome-wide association studies have uncovered more than 500 genetic variants linked to heart function, everything from heart rate to irregular rhythms that can lead to stroke, heart failure or other complications. But since most of these variations fall into areas of the genome that dont encode proteins, exactly how they influence heart function has remained unclear.
By examining heart cells derived from the skin samples of seven family members, researchers at University of California San Diego School of Medicine have now discovered that many of these genetic variations influence heart function because they affect the binding of a protein called NKX2-5.
NKX2-5 is a transcription factor, meaning it helps turn on and off genes in this case, genes involved in heart development. To do this, NKX2-5 must bind to non-coding regions of the genome. Thats where genetic variation comes in.
NKX2-5 binds to many different places in the genome near heart genes, so it makes sense that variation in the factor itself or the DNA to which it binds would affect that function, said senior author Kelly A. Frazer, PhD, professor of pediatrics and director of the Institute for Genomic Medicine at UC San Diego School of Medicine. As a result, we are finding that multiple heart-related traits can share a common mechanism in this case, differential binding of NKX2-5 due to DNA variants.
The study started with skin samples from seven people from three generations of a single family. The researchers converted the skin cells into induced pluripotent stem cells (iPSCs) as an intermediary. Like all stem cells, iPSCs can both self-renew, making more iPSCs, and differentiate into a specialized cell type. With the right cocktail of molecules and growth factors, the researchers directed iPSCs into becoming heart cells.
These heart cells actually beat in the laboratory dish, and still bear the genetic and molecular features of the individuals from which they were derived.
Frazer and team conducted a genome-wide analysis of these patient-derived heart cells. They determined that NKX2-5 can bind approximately 38,000 sites in the genome. Of those, 1,941 genetic variants affected NKX2-5 binding. The researchers investigated the role of those variants in heart gene function and heart-related traits. One of the genetic variants was associated with the SCN5A gene, which encodes the main channel through which sodium is transported in heart cells.
Since related individuals tend to share similar genetic variants, the team was able to validate their findings by analyzing the same variants in multiple samples.
People typically need a large number of samples to detect the effects of common DNA variants, so we were surprised that we were able to identify with high confidence these effects on NKX2-5 binding at so many sites across the genome with just few people, said first author Paola Benaglio, PhD, a postdoctoral researcher in Frazers lab.
Yet, she said, this finding may just be the tip of the iceberg.
There are probably a lot more genetic variants in the genome involved with NKX2-5 as well as with other important cardiac transcription factors, Frazer said. We identified almost 2,000 in this study, but thats probably only a fraction of what really exists because we were only looking at seven people in a single family and only at one transcription factor. There are probably many more variants in gene regulation sites across the entire population.
Not only does the team plan to further investigate cardiovascular genetics, but they also have their sights set on other organ systems.
We are now expanding this same model system to look at many different transcription factors, across different tissue types, such as pancreas and retina epithelia, and scaling it up to include more families, Benaglio said.
Benalgio, P. et al. (2019)Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits. Nature Genetics. DOI:https://doi.org/10.1038/s41588-019-0499-3
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Read more from the original source:
Skin-Derived Heart Cells Help Uncover the Genetic Foundations of Cardiac Function - Technology Networks
- Global Induced Pluripotent Stem Cells Market to Achieve more Profitability Ratio between 2020-2025 - Chronicle 99 - February 16th, 2020
- Cell-based meat in focus: In conversation with Meatable, Finless Foods, New Age Meats - FoodNavigator-USA.com - February 11th, 2020
- Research could be step toward lab-grown eggs and sperm to treat... - ScienceBlog.com - February 10th, 2020
- First dual stem cell therapy jointly developed by City University of Hong Kong brings new hope for cardiac repair - QS WOW News - February 10th, 2020
- Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids - Science Advances - February 10th, 2020
- AgeX Therapeutics to Collaborate with University of California, Irvine on Neural Stem Cell Research Program for Huntingtons Disease and Other... - February 4th, 2020
- 2020 Induced Pluripotent Stem Cells (iPSCs) Study: Global Markets, Technologies, Applications and Companies - Yahoo Finance - February 2nd, 2020
- Can Parkinsons be prevented as it stealthily develops? - Big Think - February 2nd, 2020
- Unpicking the proteome in single cells - Science Magazine - February 2nd, 2020
- Kyoto University team gets OK from ministry for plan to transplant iPS-derived cartilage into knee joints - The Japan Times - January 25th, 2020
- The Kyoto University team's plan to transplant iPS cartilage into knee joints is OK - gotech daily - January 25th, 2020
- Get rid of the ache within the nerves discovered with the following pointers, learn - Sahiwal Tv - January 25th, 2020
- Astellas and Adaptimmune team up in CAR-T development - European Biotechnology - January 15th, 2020
- Stem Cell Therapy Market Rising Demand for Digitization in Organizations and Growth till 2027 - Galus Australis - January 15th, 2020
- Allele and Astellas Enter into an Expanded License for the Development of iPSC Lines - Yahoo Finance - January 15th, 2020
- Researchers have managed to bio-print a functional mini-liver in 90 days - FLWL News - January 15th, 2020
- CYTOVIA Therapeutics and the New York Stem Cell Foundation Research Institute enter into a partnership to develop iPSC derived CAR NK Therapeutics -... - January 10th, 2020
- Stem Cells Market Segmentation and Analysis Report, 2025 - Food & Beverage Herald - January 10th, 2020
- Stem Cell Therapy Market Robust Growth Counted to 2025 - Instanews247 - January 10th, 2020
- The Top Biotech Trends We'll Be Watching in 2020 - Singularity Hub - January 10th, 2020
- Induced Pluripotent Stem Cells Market Structure, Industry Inspection, and Forecast 2025 - Filmi Baba - December 28th, 2019
- Top Technical Advances of 2019 - The Scientist - December 24th, 2019
- The next 3D-printing craze? It could be functioning 'mini-livers' - Inverse - December 24th, 2019
- Induced Pluripotent Stem Cells Market: Latest Innovations, Drivers and Industry Key Events 2016 2021 - Market Reports Observer - December 24th, 2019
- Stem Cell-Derived Cells Market Expected to Expand at a Steady CAGR through 2019 2029 - Downey Magazine - December 17th, 2019
- AgeX Therapeutics and Lineage Cell Therapeutics Announce Issuance of U.S. Patent for Method of Generating Induced Pluripotent Stem Cells - Yahoo... - December 11th, 2019
- Patent Granted To Lineage & AgeX - Anti Aging News - December 11th, 2019
- Charles River Announces Strategic Partnership with Bit Bio, Increasing Portfolio of Translational Drug Discovery Technologies - BioSpace - December 11th, 2019
- Fate Therapeutics Presents its First Off-the-shelf, iPSC-derived CAR T-Cell Cancer Immunotherapy Program at ASH Annual Meeting - GlobeNewswire - December 11th, 2019
- Fate Therapeutics Announces New Preclinical Data for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy - Benzinga - December 8th, 2019
- Induced Pluripotent Stem Cells Market Assessed To Tell Apart High Growth By Implies In 2018 to 2026 - Wolf Mirror - December 5th, 2019
- Kyoto University Seeking To Use Stem Cells On Knee Treatment - Anti Aging News - December 5th, 2019
- Story of a 15-year old scientist: How it all began - EuroScientist - December 5th, 2019
- Stemonix, Atomwise Team Up on Drug Discovery With MicroOrgans and AI - Xconomy - December 5th, 2019
- Channel in Nerve Cell May be Key in Unlocking Parkinson Disease Therapy - Pharmacy Times - December 3rd, 2019
- First-in-kind Human 3-dimensional Models of Parkinson's Disease and Progressive Multiple Sclerosis Launching to the International Space Station -... - December 3rd, 2019
- Stem Cells Market 2019 Global Growth Analysis and Forecast Report by 2025 - Markets Gazette 24 - November 26th, 2019
- UK animal experiment statistics indicate reluctance to embrace modern tools to advance British labs into the 21st century - Labmate Online - November 10th, 2019
- Human heart cells change during spaceflight, say scientists in study that could have far-reaching effects on c - MEAWW - November 7th, 2019
- Here's Why Fate Therapeutics Dropped as Much as 19.9% Today - Motley Fool - November 7th, 2019
- Space travel may change the human heart - Inverse - November 7th, 2019
- Allogene Therapeutics and Notch Therapeutics Announce Collaboration to Research and Develop Induced Pluripotent Stem Cell (iPSC)-Derived Allogeneic... - November 5th, 2019
- Goldfinch Bio to Present Oral and Poster Presentations at the American Society of Nephrology Kidney Week 2019 Annual Meeting - BioSpace - November 5th, 2019
- MD Anderson and Takeda Team Up on Next-Generation Immuno-Oncology Therapeutics - BioSpace - November 5th, 2019
- Induced Pluripotent Stem Cell Market is expected to witness a strong CAGR of 7.0% from 2018 to 2026 - Zebvo - November 2nd, 2019
- Can organoids, derived from stem cells, be used in disease treatments? - The Hindu - October 26th, 2019
- University team to seek approval for iPS-based heart treatment trial - The Japan Times - October 26th, 2019
- Global Gemcitabine Hydrochloride Market: Segmented By Application And Geography Trends, Growth And Forecasts To 2024 - Health News Office - October 26th, 2019
- Global consortium formed to combat unproven cell banking services - Drug Target Review - October 22nd, 2019
- Bloomberg Philanthropies, Johns Hopkins University School of Medicine, and The New York Stem Cell Foundation Research Institute Announce an... - October 22nd, 2019
- ISCT forms cell and gene therapy sector-wide coalition to combat the rise of unproven commercial cell banking services - PharmiWeb.com - October 21st, 2019
- Mutations Linked to Huntington's Increase Cells' Resistance to Manganese, Study Finds - Huntington's Disease News - October 15th, 2019
- Stem Cells Market : Insights Into the Competitive Scenario of the Market - Online News Guru - October 11th, 2019
- 'Rewind Therapeutics' and Remyelination - SciTech Europa - October 11th, 2019
- Cell Expansion Market is expected to rise at a remarkable CAGR during the Forecast Period 2016 2024 - Space Market Research - October 9th, 2019
- Global Induced Pluripotent Stem Cells Market 2019 Innovative Trends and Insights Research upto 2024 - News Adopt - October 5th, 2019
- New Rett Therapies May Stem From X-chromosome Reactivation Findings - Rett Syndrome News - October 5th, 2019
- Stemming the Tide of Alzheimer's - UCI News - October 5th, 2019
- IGIB finds a protein with better precision in gene-editing - The Hindu - October 5th, 2019
- Novel Cell Sorting and Separation Market: Focus on Acoustophoresis, Buoyancy-activated, Dielectrophoresis, Magnetophoretics, Microfluidics,... - October 5th, 2019
- Fabry Heart Cells Grown in Lab Dish Give Hints to Cardiac Complications - Fabry Disease News - September 27th, 2019
- Global Induced Pluripotent Stem Cells (iPSCs) Market 2019 Analysis & Forecast Report 2024 - Analytics News - September 24th, 2019
- Gene regulators work together for oversized impact on schizophrenia risk - National Institutes of Health - September 24th, 2019
- Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson's, Early Study Suggests - Parkinson's News Today - September 24th, 2019
- New Gene Editing Technique Shown to Correct COL7A1 Gene in RDEB Cells - Epidermolysis Bullosa News - September 24th, 2019
- Vaginitis Therapeutics Market Overview with Detailed Analysis, Competitive lands - News By ReportsGO - September 24th, 2019
- Efavirenz/Tenofovir/Emtricitabine Combination Drug Market Overview with Detailed - News by Intelligence Journal - September 24th, 2019
- Can Consciousness be Created? - University Observer Online - September 24th, 2019
- Global Induced Pluripotent Stem Cells (iPSCs) Market 2019 Industry Growth with CAGR 12.7% in Forecast to 2024 - Indian Columnist - September 21st, 2019
- Adipose Tissue-derived Stem Cells Market Size Set for Rapid Growth and Trend by2018 2028 - My Health Reporter - September 21st, 2019
- Induced Pluripotent Stem Cell Market Estimated to be Driven by Innovation and Industrialization - Analytics News - September 20th, 2019
- 2024 Projections: Induced Pluripotent Stem Cells (iPSCs) Market Report by Type, Application and Regional Outlook - TheSlapClap - September 20th, 2019
- Angelman Foundation Honors 4 for Their Research, Advocacy Efforts - Angelman Syndrome News - September 20th, 2019
- Dicerna And DCR-A1AT In Alpha-1 Antitrypsin Deficiency-Associated Liver Disease - Seeking Alpha - September 20th, 2019
- Fate Therapeutics raises $173 million in offering - The San Diego Union-Tribune - September 19th, 2019
- Induced Pluripotent Stem Cells Market is expected to reach US$ 2299.5 Mn by the end of the forecast period in 2026 - Zebvo - September 19th, 2019
- induced pluripotent stem cells (iPSCs) market reached $2.1 billion in 2016 The market should reach $3.6 billion in 2021 - ScoopJunction - September 19th, 2019
- Stem Cell-Derived Cells Market to Record an Exponential CAGR by 2025 - NewsVarsity - September 19th, 2019
- Common Prostate Drug May Slow Progression of Parkinson, Researchers Say - AJMC.com Managed Markets Network - September 19th, 2019
- Automated Large-Scale Production of Retinal Organoids - Advanced Science News - September 19th, 2019