New insights into the genetic basis of a rare type of diabetes in babies have uncovered a biological pathway that is fundamental to insulin production by pancreatic cells, and which could boost research into new treatments for more common forms of diabetes. An international research team led by scientists at the University of Exeter, the Universit Libre de Bruxelles, and the University of Helsinki, used genome sequencing to reveal that a group of babies with shared clinical features, including the development of diabetes soon after birth, all had genetic changes in the YIPF5 gene, which is involved in cell trafficking from the endoplasmic reticulum (ER) to the Golgi. The team then combined stem cell research and CRISPR gene editing to show that this gene is essential for the function of the cells that produce insulin.
The research demonstrated how the genetic changes result in high levels of stress within the cells, causing cell death, and also showed, for the first time, that YIPF5 gene function is essential for neurons and insulin-producing cells, but appears to be dispensable for the function of other cells.
Co-study lead, Elisa De Franco, PhD, from the University of Exeter, said, This study highlights the importance of gene discovery to further our understanding of fundamental mechanisms in biology. In this case, our research has resulted in the identification of a gene essential for both insulin-producing cells and neurons, highlighting a biological pathway we previously did not know was so fundamental for insulin-producing cells. This has the potential to open new avenues of research and ultimately result in a better understanding of how other types of diabetes develop.
De Franco and colleagues reported on their findings in the Journal of Clinical Investigation (JCI), in a paper titled, YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.
Neonatal diabetes develops before the age of six months, and is caused by reduced numbers of insulin-producing pancreatic cells, or impaired cell function, the authors explained. Previous research has found that neonatal diabetes is most likely caused by a mutation in a single gene, rather than presenting as an autoimmune type 1 form of the disease. To date, 30 genetic causes have been described, which account for 82% of cases, the team noted. Many patients with neonatal diabetes also have neurological symptoms, which is not surprising, the researchers continued, as cells and neurons have many genes and cellular functions in common. Pathogenic variants in 11 genes are already known to cause neonatal diabetes with neurological features, and one of the pathways known to be crucial for the function of both cells and brain cells is the endoplasmic reticulum stress response. In fact, Pathogenic variants in eight genes known to be involved in regulating the ER stress response have been found to caused diabetes (ranging from neonatal to adolescent/adult-onset diabetes), often associated with neurological features, the scientists pointed out.
To further study which genes are key to the function of insulin-producing cells, in the context of neonatal diabetes, the research team studied the genetics of almost 190 patients from all over the world who developed diabetes soon after birth. Identifying the genes causing syndromic forms of neonatal diabetes that include neurological features can highlight pathways important for development and function of -cells and neurons, giving insights into the pathogenesis of more common diseases, they noted. The results identified six babies who had neonatal diabetes and other very similar clinical featuresincluding epilepsy and microcephalyand who all exhibited mutations in the YIPF5 gene.
Researchers at the Universit Libre de Bruxelles and the University of Helsinki then carried out a series of studies in insulin-producing cells and in stem cells to try to understand the function of YIPF5 in the insulin-producing cells. We used three human cell models (YIPF5 silencing in EndoC-H1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects cells, the investigators explained. Their results showed that when the gene was lacking, or had the same mutations as those found in the neonatal diabetes patients, the insulin-producing cells couldnt function normally to produce enough insulin. And an attempt to cope with this malfunction the cells activated stress mechanisms, which ultimately resulted in cell death. YIPF5 deficiency reduces -cell survival by enhancing the ER stress response and sensitizing human -cells to ER stress-induced apoptosis, they commented.
Co-senior study author Timo Otonkoski, from the University of Helsinki, explained, Using the CRISPR gene scissor DNA-editing technology we could correct the patient mutation in stem cells in order to fully understand its effects. The combination of gene editing with stem cells provides powerful new tools for the study of disease mechanisms. Colleague and co-senior author, Miriam Cnop, PhD, from the Universit Libre de Bruxelles, continued, The possibility to generate insulin-producing cells from stem cells has given us the possibility to study what goes wrong in cells from patients with this rare form and also other types of diabetes. It is an extraordinary disease-in-a-dish model to study mechanisms of disease and test treatments.
The teams study results offer new insights into which cellular steps are important for making insulin, and for maintaining the function of insulin-producing cells in the pancreas. This insight could help researchers develop better therapies to treat patients with common types of diabetes that affect 460 million people worldwide.
To the best of our knowledge, this is the first report of mutations in a gene affecting ER-to-Golgi trafficking resulting in diabetes by increasing -cell ER stress, uncovering a critical role of YIPF5 in the human -cell, the authors reported. Our findings highlight a biological pathway essential for -cells.
We are very grateful to the patients, their families, and their doctors for their participation in the study, noted Andrew Hattersley, PhD, one of the senior authors of the study, from the University of Exeter. Without them, we could not have accomplished this. It is our wish that further research will benefit the patients, to facilitate diagnosis and treatment of their diabetes.
Anna Morris, assistant director of research strategy and partnerships at Diabetes UK, which provided funding for the studies, said, These findings provide important new information on how beta cells in the body manufacture insulin and what happens when this process goes wrong. Understanding more about how rarer forms of diabetes develop brings us closer to discovering new ways to cure and prevent all forms of the condition. This is a key part of Diabetes UKs new strategy, and we are proud to have funded De Francos vital research.
- Induced Pluripotent Stem Cells Market Exclusive insight on Transformation 2029 Clark County Blog - Clark County Blog - April 20th, 2021
- Global Stem Cell Technologies and Applications Market 2020-2030 - GlobeNewswire - April 16th, 2021
- Global Human Embryonic Stem Cells Industry Market 2021 In-depth Industry Analysis, Growth By 2027:Lonza Group Ltd., Life Technologies Corporation,... - April 6th, 2021
- Human Embryonic Stem Cells (HESC) Market 2021 Is Rapidly Increasing Worldwide in Near Future | Top Companies Analysis- ESI BIO, Thermo Fisher,... - April 6th, 2021
- Scientists grow and observe mouse embryos outside the womb - ISRAEL21c - April 6th, 2021
- New Michigan law requires those receiving Johnson & Johnson vaccine be told it was developed using stem cells | TheHill - The Hill - April 6th, 2021
- Stem Cell Therapy Market Latest Innovations and Trends to Boost Growth during 2021-2028 | Astellas Pharma Inc, Cellular Engineering Technologies,... - April 6th, 2021
- Xenobots 2.0 are Here and Still Developed With Frog Stem Cells - Unite.AI - April 6th, 2021
- Induced Pluripotent Stem Cells Market Exclusive insight on Transformation 2029 SoccerNurds - SoccerNurds - March 29th, 2021
- Human Embryonic Stem Cells | The Embryo Project Encyclopedia - March 24th, 2021
- Sydney archbishop urges 'deep breath' after news of artificial embryos - Long Island Catholic - March 24th, 2021
- Researchers grow mouse embryos outside the uterus to reveal hidden growth stages - SlashGear - March 20th, 2021
- Industry Overview of Stem Cell Treatments: Market Report Based on Development, Scope, Share, Trends, Forecast to 2026 SoccerNurds - SoccerNurds - March 15th, 2021
- A Genetic Curse, a Scared Mom, and the Quest to 'Fix' Embryos - WIRED - March 13th, 2021
- Deciphering epiblast lumenogenesis reveals proamniotic cavity control of embryo growth and patterning - Science Advances - March 11th, 2021
- Promising stem-cell based drug for treatment of ALS receives patent - The Jerusalem Post - March 11th, 2021
- Human embryo research beyond the primitive streak - Science Magazine - March 11th, 2021
- Detroit mayor turned down J&J vaccine in favor of others - WCNC.com - March 11th, 2021
- 14 Advantages and Disadvantages of Embryonic Stem Cell ... - March 7th, 2021
- Embryonic stem cell | biology | Britannica - March 7th, 2021
- Is the coronavirus vaccine made from fetal cell lines? - March 7th, 2021
- Effect of Nanog overexpression on the metastatic potential of a mouse melanoma cell line B16-BL6 - DocWire News - March 7th, 2021
- Gene behind third of cancers turned off by scientists - Yahoo Sports - March 3rd, 2021
- Comprehensive Report on Human Embryonic Stem Cells Market 2021 | Size, Growth, Demand, Opportunities & Forecast To 2027 | CellTherapies P/L,... - March 3rd, 2021
- Stem Cell Therapy Market 2021 Global Industry Size, Reviews, Segments, Revenue, and Forecast to 2027 NeighborWebSJ - NeighborWebSJ - March 1st, 2021
- Innovative Stem Cells Market Research Report Segmented by Applications, Geography, Trends and Projection 2026 Express Keeper - Express Keeper - March 1st, 2021
- Human Embryonic Stem Cells Industry Market 2021 Overview, Opportunities, In-Depth Analysis by 2027:Lonza Group Ltd., Life Technologies Corporation,... - February 25th, 2021
- Stem Cell Therapy Market Size 2021 | Analysis, Regional Outlook, Competitive Strategies And Forecast up to 2027 - NY Market Reports - February 25th, 2021
- Global Cell Freezing Media for Cell Therapy Market Size, Analysis, Growth ratio, Top Players and Fut - PharmiWeb.com - February 25th, 2021
- The Very First Signs of an Immune Response Have Been Filmed in a Developing Embryo - ScienceAlert - February 14th, 2021
- Outlook on the Cell Therapy Global Market to 2027 - Opportunity Analysis and Industry Forecasts - Yahoo Eurosport UK - February 10th, 2021
- Translational Regenerative Medicine Market: Immunotherapy is projected to be the fastest growing segment during the forecast period - BioSpace - February 10th, 2021
- Study identifies major flaws in iBMEC-based models of the blood-brain barrier - News-Medical.Net - February 10th, 2021
- Harnessing the Potential of Cell and Gene Therapy - OncLive - February 5th, 2021
- When scientific data is too good to be true - Haaretz - February 5th, 2021
- Global Human Embryonic Stem Cells Market increasing demand with Industry Professionalist |know the Brand Players forecast 2027 Jumbo News - Jumbo... - February 5th, 2021
- Should We Double The Age When Science Can Experiment On Babies? - 550 KTSA - February 5th, 2021
- Push on to Allow Expanded Human-Embryo Research - National Review - February 3rd, 2021
- Missouri State Representative Indicted Over Alleged Stem Cell Therapy Scam - IFLScience - February 3rd, 2021
- ToolGen ties up with 3D bioprinting company to apply induced pluripotent stem cells to gene correction - Aju Business Daily - February 3rd, 2021
- Stem Cells Market is Expected to Thrive at Impressive CAGR by 2025 Murphy's Hockey Law - Murphy's Hockey Law - February 3rd, 2021
- Louisiana Right to Life: COVID-19 vaccines and abortion - The Baptist Message - January 16th, 2021
- Organoids show how mutations in top autism gene may lead to brain overgrowth in people - Spectrum - January 16th, 2021
- Reversing The Aging Clock With Epigenetic Reprogramming - Bio-IT World - January 16th, 2021
- Global Stem Cell Therapy Market Report 2020: Market to Recover and Reach $14.76 Billion in 2023 at a CAGR of 19.62% - Forecast to 2030 - Yahoo Finance - January 8th, 2021
- Factor Bioscience spins out a new cell therapy player with eyes on the clinic within 2 years - Endpoints News - January 8th, 2021
- 'He was very honored in his work' - Mercer Island Reporter - December 28th, 2020
- Stem Cell Assay Market In-Depth Analysis and Forecast 2017-2025 - NeighborWebSJ - December 25th, 2020
- Israeli biotech firm's ALS treatment shows safety of use in trials - The Jerusalem Post - December 18th, 2020
- Ca Bishops To Work w/ Govt on Vaccination Campaigns - Catholic Herald Online - December 15th, 2020
- Advanced Therapy Medicinal Products Market 2019 Global Industry Analysis By Size, Share, Trends and - PharmiWeb.com - December 10th, 2020
- Accelerating Sales in North America to Drive the Stem Cell Therapy market between 2020 and 2030 - Cheshire Media - December 3rd, 2020
- Human Embryonic Stem Cells Market in Global : Current and the Future Trends: Astellas Pharma Inc/ Ocata Therapeutics, Stemcell Technologies Inc - The... - December 3rd, 2020
- Stem Cells Market Size on Target to Reach US$ 17.79 Billion 2027 - Cheshire Media - December 3rd, 2020
- GFI1: New Role Uncovered for a Protein Involved in Hearing : The Hearing Journal - LWW Journals - December 3rd, 2020
- Human Embryonic Stem Cells (HESC) Market 2019 | Analyzing The Impact Followed By Restraints, Opportunities And Projected Developments | DataIntelo -... - December 1st, 2020
- Stem Cell Manufacturing Market Analysis by Industry Size, Share, Key Drivers, Growth Factors, Demands, Top Manufacturers- Merck Group, Becton,... - December 1st, 2020
- Stem Cells Market is Expected to Thrive at Impressive CAGR by 2025 - The Haitian-Caribbean News Network - December 1st, 2020
- This Date in UCSF History: Election Offers Mixed Bag of Results - Synapse - December 1st, 2020
- Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19) - Cheshire Media - December 1st, 2020
- Stem Cell Assay to Register Substantial Expansion by 2026| Merck, Thermo Fisher Scientific, GE Healthcare - The Haitian-Caribbean News Network - December 1st, 2020
- Autism genes affect development of neurons and glia - Spectrum - November 28th, 2020
- Stem Cell Medical Research to Expand in California Following Passage of Prop. 14 - Times of San Diego - November 28th, 2020
- TRF2-mediated telomere protection is dispensable in pluripotent stem cells - Nature.com - November 26th, 2020
- Stem Cell Therapy Global Market Report 2020-30: Covid 19 Growth and Change - Yahoo Finance UK - November 26th, 2020
- Stem Cells Market 2020: Rising with Immense Development Trends across the Globe by 2027 - The Market Feed - November 26th, 2020
- Stem Cell Characterization and Analysis Tool Market 2020: Potential growth, attractive valuation make it is a long-term investment | Know the COVID19... - November 26th, 2020
- Global Regenerative Medicine Market 2020-2025: Opportunities with the Implementation of the 21st Century Cures Act - Yahoo Eurosport UK - November 26th, 2020
- Mount Sinai Cardiologist Awarded $2.9 Million NIH Grant to Advance Work with Stem Cells and Heart Repair after Heart Attack - Cath Lab Digest - November 25th, 2020
- Dr. David Steenblock - Stem Cells and Regenerative Medicine - BlogTalkRadio - November 25th, 2020
- Breakthroughs in Stem Cell Based Treatment of Heart Disease - The Connecticut College Voice - November 25th, 2020
- Stem Cell Therapy Market To Observe Exponential Growth By 2020-2027 | Reports Globe - Cheshire Media - November 25th, 2020
- The Stem Cell Characterization and Analysis Tools Market to grow incomparably in the next decade - The Market Feed - November 25th, 2020
- University of Alberta research team poised to cure diabetesagain - Wetaskiwin Times Advertiser - November 23rd, 2020
- New Role For Serotonin Identified In The Evolution Of The Developing Brain - Anti Aging News - November 18th, 2020
- AgeX Therapeutics Reports Third Quarter 2020 Financial Results and Provides Business Update - Business Wire - November 18th, 2020
- Stem Cell Banking Market is Projected to Reach $6,956 million by 2023 | Leading key players are Cord Blood Registry, ViaCord, Cryo-Cell, China Cord... - November 14th, 2020
- California approves billions for stem-cell research - Modern Healthcare - November 14th, 2020
- Cell Freezing Media for Cell Therapy Market 2020 Strategic Assessment BioLife Solutions, Thermo Fisher Scientific, GE Healthcare - KYT24 - November 14th, 2020
- The heart of a mouse embryo was first created from stem cells - FREE NEWS - November 11th, 2020