Monday, September 23, 2019
Modeled gene expression changes match those found in patients brains.
Researchers have discovered that gene expression regulators work together to raise an individuals risk of developing schizophrenia. Schizophrenia-like gene expression changes modeled in human neurons matched changes found in patients brains. The researchers, led by Kristen Brennand, of the Icahn School of Medicine at Mount Sinai, New York City, report on their findings in Nature Genetics. The work was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.
Genome-wide association studies have revealed at least 143 chromosomal sites associated with risk for schizophrenia. However, individually, each of these sites can explain only a small fraction of the risk. Even when the effects of disease-linked rare genetic variants are factored in, most of schizophrenias known high inheritance remains unexplained. One possible clue: more than 40% of the suspect chromosomal sites contain regulators, called expression quantitative trait loci, or eQTLs, that govern the expression of multiple genes.
Individually, these gene regulators have a modest effect on the brain. Working in concert, they exert different and more significant effects on the brain effects that boost schizophrenia risk, explained David Panchision, chief of the Developmental Neurobiology Program at NIMH. Learning more about the downstream cellular and molecular effects of such synergy holds hope for advances in precision psychiatry and more personalized medicine.
To explore the role of these regulators, Brennand and colleagues studied them in induced neurons using a molecular modeling technology. This induced pluripotent stem cell method makes it possible to grow a persons unique neurons in a petri dish using stem cells derived from their skin cells. The researchers used the model to take a closer look at the downstream molecular consequences of gene expression changes known to occur in schizophrenia, and compared them with changes seen in postmortem brains and similarly modeled neurons of people with the illness.
The researchers experimentally mimicked the interaction of multiple risk genes thought to contribute to schizophrenia. They used the gene editing tool CRISPR to simultaneously increase or decrease expression of four schizophrenia-implicated genes known to harbor eQTLs. The genes were selected because they were deemed most likely to confer disease risk by regulating gene expression. To trigger changes in the direction predicted to heighten risk for schizophrenia, expression was increased for three of the genes and decreased for one.
Manipulating expression of the four genes altered expression of 1,261 other genes 665 increased and 596 decreased. This was many more than would be expected if the genes had been merely acting individually, suggesting an underlying mechanism that is synergistic rather than additive.
This unexpected synergy between gene variants demonstrated how even subtle genetic variations can impact neuronal function, said Brennand. These interactions emphasize the importance of considering the complex nature of schizophrenia and other psychiatric disorders, where a combination of gene variants contributes to disease.
Many of the genes affected downstream contained variants that had been linked to autism spectrum disorder or bipolar disorder, in addition to schizophrenia consistent with other research suggesting genetic overlap across mental disorders.
The experimentally induced gene expression changes mirrored those seen in postmortem brains of people with the three mental illnesses. The same changes were also seen in induced pluripotent stem cell neurons from people with childhood-onset schizophrenia, a rare form of the illness thought to be more genetic in origin.
Notably, all of these gene changes resulted in loss-of-brain-function effects when screened one-at-a-time in a zebrafish model, said Brennand. We have added several of them to a list of genes worthy of further study for possible involvement in schizophrenia. There is an overwhelming need for future studies to similarly model such multi-gene interactions in complex cells and circuits.
About the National Institute of Mental Health (NIMH):The mission of theNIMHis to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit theNIMH website.
About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
NIHTurning Discovery Into Health
Schrode N, Ho S-M, Yamamuro K, Dobbyn A, Huckins L, Matos MR. Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics, September 23, 2019.DOI: 10.1038/s41588-019-0497-5
- Repairing the Brain With Stem Cells? A Conversation With Prof. Jack Price - Being Patient - December 3rd, 2020
- Global Induced Pluripotent Stem Cells Market Size, Comprehensive Analysis, Development Strategy, Future Plans and Industry Growth with High CAGR by... - December 3rd, 2020
- Industry Verticals: Induced Pluripotent Stem Cells (iPSC) Market Latest and updated Scope and Application 2020-2027 - The Blend - December 3rd, 2020
- Bayer Launches Cell and Gene Therapy Platform to Maximize Recent Acquisitions - PharmaLive - December 3rd, 2020
- Stem Cells Market Size on Target to Reach US$ 17.79 Billion 2027 - Cheshire Media - December 3rd, 2020
- Bayer establishes Cell and Gene Therapy Platform to accelerate pharmaceutical innovation | More News | News Channels - PipelineReview.com - December 3rd, 2020
- Growing Value of Stem Cells in Medicine to Create a US$2,4 Billion Opportunity for Induced Pluripotent Stem Cell ((iPSC) - GlobeNewswire - November 27th, 2020
- Induced Pluripotent Stem Cells Market New Research Study Report with Size, Share, Trends, Emerging Applications, Opportunities and Worldwide Analysis... - November 27th, 2020
- Induced Pluripotent Stem Cells (iPSCs) Market Applications, Types and Future Ou - News by aeresearch - November 27th, 2020
- Research Paper Showing ProtoKinetix AAGP Enhanced Stem Cell Derived Retina Precursor Cells Restoration of Vision - Business Wire - November 27th, 2020
- Induced Pluripotent Stem Cells Market 2020: Enhanced Growth, Recent Trends and Major Companies are Fujifilm Holding Corporation, Astellas Pharma, Fate... - November 27th, 2020
- The Stem Cell-Derived Cells market to Scale new heights in the next decade - Khabar South Asia - November 27th, 2020
- Astronaut Soichi Noguchi still adapting to life on ISS - The Japan Times - November 27th, 2020
- Potential new therapies for Alzheimer's disease are revealed through network modeling of its complex molecular interactions - Science Codex - November 27th, 2020
- Global Induced Pluripotent Market To Perceive Biggest Trend And Opportunity With Key Players CELGENE CORPORATION; Astellas Pharma Inc.; Thermo Fisher... - November 22nd, 2020
- Global Stem Cell Banking Market 2020: Overview, Trends, Opportunities, Impact of Drivers, Key Vendors, Types, Applications, Forecast by Focusing... - November 22nd, 2020
- Thanyapura, StemCells21 to offer premium stem cell treatments in Thailand - BSA bureau - November 20th, 2020
- Neurons stripped of their identity are hallmark of Alzheimer's disease, study finds - National Science Foundation - November 20th, 2020
- Fred Hutch at ASH: Fauci fireside chat, latest on cell therapies, repairing immune function, COVID and clots and more - Newswise - November 20th, 2020
- Stem Cells Market Value Expected To Reach $17.79 Billion By 2027 - Eurowire - November 20th, 2020
- How regenerative medicine could be used to contain COVID-19, others - Guardian - November 20th, 2020
- The Induced Pluripotent Stem Cells Market To Witness Fierce Competition Amongst The Key Players - KYT24 - November 18th, 2020
- at ASH: Fauci fireside chat, latest on cell therapies, repairing immune function, COVID and clots and more - Fred Hutch News Service - November 18th, 2020
- Neurons stripped of their identity are hallmark of Alzheimers disease, study finds - Newswise - November 18th, 2020
- Genetic influences on viral-induced cytokine responses in the lung - DocWire News - November 18th, 2020
- Japanese and U.S. astronauts arrive at ISS in SpaceX ship - The Japan Times - November 18th, 2020
- AgeX Therapeutics Reports Third Quarter 2020 Financial Results and Provides Business Update - BioSpace - November 18th, 2020
- Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia -... - November 12th, 2020
- Induced Pluripotent Stem Cells (iPSCs) Market Size, Drivers, Potential Growth Opportunities, Competitive Landscape, Trends And Forecast To 2027 -... - November 12th, 2020
- Proteintech and HebeCell Announce Collaboration on Nanobody iPSC-derived Natural Killer Cells - BioSpace - November 12th, 2020
- Global Induced Pluripotent Stem Cells Market Analysis Trends, Growth Opportunities, Size, Type, Dynamic Demand and Drives with Forecast to 2026 -... - November 12th, 2020
- Stem Cell Manufacturing Market Share & Size, Future Growth, Trends Evaluation, Demands, Regional Analysis and Forecast to 2027| Merck Group,... - November 12th, 2020
- Induced Pluripotent Stem Cells Market Comprehensive Insights, Growth, Forecast and Covid-19 Impact by 2026 | Medipost Co. Ltd., Ocata Therapeutics... - November 12th, 2020
- Induced Pluripotent Stem Cells Industry Market 2020 Global Trends, Key Players, Share, Growth, Analysis, Opportunities and Forecast To 2026 -... - October 31st, 2020
- The Stem Cell-Derived Cells market to be in conjunction to growth from 2020 to 2030 - PRnews Leader - October 31st, 2020
- In Vitro Toxicology Testing Market: Facts, Figures and Analytical Insights, 2018 to 2024 - Aerospace Journal - October 31st, 2020
- Bayer Acquires AskBio to Expand Gene Therapy Platform - PharmaLive - October 31st, 2020
- Global Induced Pluripotent Stem Cells (iPSCs) Market 2020 with COVID-19 After Effects Growth Drivers, Top Key Players, Industry Segments and Forecast... - October 29th, 2020
- Induced Pluripotent Stem Cells (iPSCs) Market 2019 | How The Industry Will Witness Substantial Growth In The Upcoming Years | Exclusive Report By... - October 29th, 2020
- Global Induced Pluripotent Stem Cells Market Analysis by Size: 2025, Impact of Covid-19 on Industry Chain, Market Growth, Drivers | Business Overview... - October 29th, 2020
- The Induced Pluripotent Stem Cells Market To Witness A Major Breakthrough In The Form Of A Double-Digit CAGR Of 7% - KYT24 - October 29th, 2020
- Emulate Signs Collaborative Agreement with the FDA to Apply Lung-Chip to Evaluate Safety of COVID-19 Vaccines and Protective Immunity Against... - October 29th, 2020
- QurAlis Announces Appointment of New Chief Medical Officer and Formation of Clinical Advisory Board - BioSpace - October 29th, 2020
- AgeX Therapeutics Sublicenses Stem Cell Line ESI-053 to ImStem Biotechnology for Development of Cell Therapy Candidate IMS001 for COVID-19 and Acute... - October 29th, 2020
- Bayer Acquires AskBio for Up to $4 Billion to Expand Gene Therapy Platform - BioSpace - October 29th, 2020
- How Will the Virus Epidemic Cause Induced Pluripotent Stem Cells (iPSCs) Market 2020 - The Think Curiouser - October 24th, 2020
- Trends in the Ready To Use Induced Pluripotent Stem Cells Market 2020-2020 - Eurowire - October 24th, 2020
- Stem Cell-Derived Cells Market to Expand at a Healthy CAGR of XX% Between and 2019 2029 - Eurowire - October 24th, 2020
- The Induced Pluripotent Stem Cells Market To Mark Robustness In The Form Of A Robust CAGR - KYT24 - October 23rd, 2020
- COVID-19 can affect the heart - Science Magazine - October 23rd, 2020
- Kobe Hospital Trials Transplant to Reverse Blindness A First in the World - JAPAN Forward - October 23rd, 2020
- Rethinking the Link between Cannabinoids and Learning - Lab Manager Magazine - October 23rd, 2020
- Cold sore virus can spread to unborn babies harming their brains, docs warn - The Sun - October 23rd, 2020
- Microscopy Beyond the Resolution Limit - Lab Manager Magazine - October 21st, 2020
- AMSBIO Launches New Human iPSC-Derived Cells and iPSC Differentiation Reagent Kits - Technology Networks - October 20th, 2020
- Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 - The Think Curiouser - October 20th, 2020
- Groundbreaking eye surgery in Kobe offers hope to sight impaired : The Asahi Shimbun - Asahi Shimbun - October 20th, 2020
- Induced Pluripotent Stem Cells (iPSCs) Industry 2020 Includes The Major Application Segments And Size In The Global Market To 2026 - PRnews Leader - October 16th, 2020
- Induced Pluripotent Stem Cells Market 2020 Is Slated to Grow Rapidly in the Forthcoming Years with Key Players Addgene, Axol Bioscience, Cell... - October 16th, 2020
- Disruptive Technologies and Mature Regulatory Environment Vital for Cell Therapy Maturation - BioSpace - October 16th, 2020
- Novellus Therapeutics Exclusively Licenses Induced Mesenchymal Stem Cells (iMSCs) to NoveCite for COVID-19 Related Acute Respiratory Distress Syndrome... - October 16th, 2020
- Brain organoids reveal neuronal flaws in syndrome tied to autism - Spectrum - October 16th, 2020
- Manufacturing a Personalized Cellular Universe: 3D Bioprinting in the Biotech Industry - BioSpace - October 16th, 2020
- Fate Therapeutics Announces Presentations at the 2020 Society for Immunotherapy of Cancer Annual Meeting - GlobeNewswire - October 16th, 2020
- Global Stem Cell Therapy Market 2020: Trends, and Opportunity Analysis, Top Manufacturers And Forecast to 2027 - PRnews Leader - October 16th, 2020
- Cytovia Therapeutics partners with Inserm to develop selective CD38 NK therapeutics and offer new treatment options for Multiple Myeloma patients |... - October 8th, 2020
- Dolly the Sheep: '90s Media Sensation - Mental Floss - October 8th, 2020
- Regeneron, Pfizer and BioNTech Accused of Infringing Allele Patent in Connection with COVID-19 Technologies - IPWatchdog.com - October 8th, 2020
- Yufan inks deal with Abound to develop antibodies directing CAR T cells against cancer targets - BioWorld Online - October 7th, 2020
- Allele Biotechnology and Pharmaceuticals Files Two Lawsuits for Patent Infringement for the Unauthorized Use of mNeonGreen in Development and Testing... - October 7th, 2020
- Huge Investment in Induced Pluripotent Stem Cells Market Expected to Witness the Highest Growth 2026 | Fujifilm Holding Corporation (CDI) Ncardia,... - October 3rd, 2020
- Stem Cell-Derived Cells Market Forecasted To Surpass The Value Of US$ XX Mn/Bn By 2019 - 2029 - Stock Market Funda - October 3rd, 2020
- Kyoto University project aims to supply iPS cells widely at low cost - The Japan Times - September 29th, 2020
- ONLINE: The Future of Medicine - Isthmus - September 29th, 2020
- funded study sheds light on abnormal neural function in rare genetic disorder - National Institutes of Health - September 29th, 2020
- Stem Cell Market Potential Growth, Size, Share, Demand and Analysis of Key Players Research Forecasts to 2027 - The Daily Chronicle - September 29th, 2020
- The new pharma collaborations driving transformative research in oncology - - pharmaphorum - September 29th, 2020
- Global Induced Pluripotent Stem Cells (iPSCs) Market 2020 Manufacturer Analysis, Technology Advancements, Industry Scope and Forecast to 2027||Fate... - September 21st, 2020
- Induced Pluripotent Stem Cells Market to Witness Huge Growth by 2025| Bone Therapeutics SA, System Biosciences, Axiogenesis, Regeneus Ltd.,... - September 14th, 2020
- Global Stem Cells Market Report, History And Forecast 2020-2027, Breakdown Data By Manufacturers, Key Regions, Types And Application - Bulletin Line - September 11th, 2020