A protein that helps make neurons also works to reprogram scar tissue cells into heart muscle cells, especially in partnership with a second protein, according to a study led by Li Qian, PhD, at the UNC School of Medicine.
CHAPEL HILL, N.C. Scientists at the UNC School of Medicine have made a significant advance in the promising field of cellular reprogramming and organ regeneration, and the discovery could play a major role in future medicines to heal damaged hearts.
In a study published in the journal Cell Stem Cell, scientists at the University of North Carolina at Chapel Hill discovered a more streamlined and efficient method for reprogramming scar tissue cells (fibroblasts) to become healthy heart muscle cells (cardiomyocytes). Fibroblasts produce the fibrous, stiff tissue that contributes to heart failure after a heart attack or because of heart disease. Turning fibroblasts into cardiomyocytes is being investigated as a potential future strategy for treating or even someday curing this common and deadly condition.
Surprisingly, the key to the new cardiomyocyte-making technique turned out to be a gene activity-controlling protein called Ascl1, which is known to be a crucial protein involved in turning fibroblasts into neurons. Researchers had thought Ascl1 was neuron-specific.
Its an outside-the-box finding, and we expect it to be useful in developing future cardiac therapies and potentially other kinds of therapeutic cellular reprogramming, said study senior author Li Qian, PhD, associate professor in the UNC Department of Pathology and Lab Medicine and associate director of the McAllister Heart Institute at UNC School of Medicine.
Scientists over the last 15 years have developed various techniques to reprogram adult cells to become stem cells, then to induce those stem cells to become adult cells of some other type. More recently, scientists have been finding ways to do this reprogramming more directly straight from one mature cell type to another. The hope has been that when these methods are made maximally safe, effective, and efficient, doctors will be able to use a simple injection into patients to reprogram harm-causing cells into beneficial ones.
Reprogramming fibroblasts has long been one of the important goals in the field, Qian said. Fibroblast over-activity underlies many major diseases and conditions including heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, and the scar-like brain damage that occurs after strokes.
In the new study, Qians team, including co-first-authors Haofei Wang, PhD, a postdoctoral researcher, and MD/PhD student Benjamin Keepers, used three existing techniques to reprogram mouse fibroblasts into cardiomyocytes, liver cells, and neurons. Their aim was to catalogue and compare the changes in cells gene activity patterns and gene-activity regulation factors during these three distinct reprogrammings.
Unexpectedly, the researchers found that the reprogramming of fibroblasts into neurons activated a set of cardiomyocyte genes. Soon they determined that this activation was due to Ascl1, one of the master-programmer transcription factor proteins that had been used to make the neurons.
Since Ascl1 activated cardiomyocyte genes, the researchers added it to the three-transcription-factor cocktail they had been using for making cardiomyocytes, to see what would happen. They were astonished to find that it dramatically increased the efficiency of reprogramming the proportion of successfully reprogrammed cells by more than ten times. In fact, they found that they could now dispense with two of the three factors from their original cocktail, retaining only Ascl1 and another transcription factor called Mef2c.
In further experiments they found evidence that Ascl1 on its own activates both neuron and cardiomyocyte genes, but it shifts away from the pro-neuron role when accompanied by Mef2c. In synergy with Mef2c, Ascl1 switches on a broad set of cardiomyocyte genes.
Ascl1 and Mef2c work together to exert pro-cardiomyocyte effects that neither factor alone exerts, making for a potent reprogramming cocktail, Qian said.
The results show that the major transcription factors used in direct cellular reprogramming arent necessarily exclusive to one targeted cell type.
Perhaps more importantly, they represent another step on the path towards future cell-reprogramming therapies for major disorders. Qian says that she and her team hope to make a two-in-one synthetic protein that contains the effective bits of both Ascl1 and Mef2c, and could be injected into failing hearts to mend them.
Cross-lineage Potential of Ascl1 Uncovered by Comparing Diverse Reprogramming Regulatomes was co-authored by Haofei Wang, Benjamin Keepers, Yunzhe Qian, Yifang Xie, Marazzano Colon, Jiandong Liu, and Li Qian. Funding was provided by the American Heart Association and the National Institutes of Health (T32HL069768, F30HL154659, R35HL155656, R01HL139976, R01HL139880).
Media contact: Mark Derewicz, 919-923-0959
The rest is here:
Scientists Discover Protein Partners that Could Heal Heart Muscle | Newsroom - UNC Health and UNC School of Medicine
- Israeli-Based 3D-Printed Lab-Grown Meat Company is Building World's ... - December 27th, 2022
- Global Synthetic Stem Cells Market Is Expected To Reach Around USD 42 Million By 2025 - openPR - October 13th, 2022
- A Look Into the Next Century After 100 Years of Insulin - Cureus - October 13th, 2022
- Grafting and Budding Nursery Crop Plants - North Carolina State University - October 4th, 2022
- Lifting up NC Teachers of the Year and TFA alumni - EdNC - August 22nd, 2022
- Vegan Oysters in Shells? This Startup Just Developed a Prototype to Save the Oceans - VegNews - July 27th, 2022
- How psilocybin, the psychedelic in mushrooms, may rewire the brain to ease depression, anxiety and more - KYMA - July 19th, 2022
- Inceptor Bio Announces Strategic Collaboration with University of Minnesota to Develop Novel iPSC Platform for the Advancement of Next-Generation... - July 3rd, 2022
- W-S organization working on regenerative therapies for 40 organs, tissues - WRAL TechWire - July 3rd, 2022
- BioRestorative Therapies Annou - GuruFocus.com - July 3rd, 2022
- How psilocybin, the psychedelic in mushrooms, may rewire the brain to ease depression, anxiety - WYFF4 Greenville - June 13th, 2022
- Pediatric Urologist Dr. Anthony Atala to Receive 2022 Jacobson Innovation Award of the American College of Surgeons for Pioneering Work in... - June 13th, 2022
- The Soybean Plant | NC State Extension Publications - June 4th, 2022
- A Cure for Type 1 Diabetes? For One Man, It Seems to Have Worked. - June 4th, 2022
- Jasper Therapeutics to Present Updated Data on JSP191 Conditioning in SCID Patients at the 2022 Clinical Immunology Society Annual Meeting - Yahoo... - April 6th, 2022
- Hoth Therapeutics Announces a Sponsored Research Agreement to Further Develop Novel mRNA Cancer Therapeutic HT-KIT - Yahoo Finance - November 22nd, 2021
- Cytovia and Cellectis Expand Their TALEN Gene-Edited iNK Partnership to Enable Broader ... - The Bakersfield Californian - November 22nd, 2021
- Study Underway to Evaluate New PD-1/CD3 Antibody in T-cell Lymphoma - Targeted Oncology - October 28th, 2021
- What it means to be the worlds first IVF baby - THE WEEK - August 31st, 2021
- Cellectis Announces Participation in Five Investor Conferences - Yahoo Finance - August 31st, 2021
- Nanodecoy Therapy is an Effective Alternative to Neutralize SARS-CoV-2 Virus - AZoNano - June 23rd, 2021
- 'Nanodecoy' Therapy Binds and Neutralizes SARS-CoV-2 Virus - NC State News - June 23rd, 2021
- Researchers curb local immune response in horses receiving stem cell injury therapy - Horsetalk - February 7th, 2021
- After Bone Marrow Donation Saves 9-Year-Old Boy With Cancer, Boston Mom Fights To Raise Awareness - Here And Now - February 7th, 2021
- Invisible pest causes more than $1 billion in crop losses - The Albany Herald - January 13th, 2021
- Bayer to acquire Asklepios Bio in foray into gene therapy worth up to $4 billion - Reuters - January 13th, 2021
- Chancellor Harold L. Martin, on His Plan to Safely Open the Nation's Largest HCBU During COVID-19 - TIME - August 23rd, 2020
- Inside the race to ditch formula and grow breast milk in the lab - Wired.co.uk - August 23rd, 2020
- Study finds little evidence to back cord-blood therapy for autism - Spectrum - June 12th, 2020
- Balding men could grow hair back in weeks thanks to 'miracle potion' - Daily Star - May 19th, 2020
- Treatment in clinical trial offers options to woman fighting return of cancer (+ video) - WRAL Tech Wire - February 28th, 2020
- Searching for the 'big break' that could turn stem cells into a weapon against dementia - Genetic Literacy Project - February 28th, 2020
- Why Some COVID-19 Cases Are Worse than Others - The Scientist - February 28th, 2020
- The Future of Bioprinting Research Has a New Road Map - 3DPrint.com - February 14th, 2020
- Top Florida Medical Spa, Amnion of Florida, Partners With Merakris Therapeutics to Advance Their Non-Surgical Treatment Options - Business Wire - December 11th, 2019
- Synthetic Stem Cells Market Is Expecting Revolutionary Growth 2019 with Top Key Players: North Carolina State University (NCSU), Zhengzhou University... - December 6th, 2019
- Clinic pitches unproven treatments to desperate patients, with tips on raising the cash - Seattle Times - December 6th, 2019
- Reviewing vTv Therapeutics Inc. (VTVT)'s and Asterias Biotherapeutics Inc. (:)'s results - MS Wkly - October 27th, 2019
- Reviewing BioCryst Pharmaceuticals Inc. (BCRX)'s and Brainstorm Cell Therapeutics Inc. (NASDAQ:BCLI)'s results - MS Wkly - October 27th, 2019
- Global Synthetic Stem Cells Market Estimated to Reach USD 42 Million By 2025 - Daily Market Updates - September 29th, 2019
- Global Synthetic Stem Cells Market to Accumulate Revenues Worth US $42 Million By 2025 - ZMR News Research - September 24th, 2019
- Heal Yourself: How Exosome Therapy Can Repair Age-Damaged Skin - Market Research Finance - September 24th, 2019
- Cesca Therapeutics Inc. (KOOL) Can't Be More Safe. Trades Significantly Higher - Invest Tribune - September 24th, 2019
- Stem Cell Winston Salem North Carolina 27150 - April 5th, 2019
- Clinical Trial for Autism - cordbloodbank.com - March 8th, 2019
- Stem Cell Chapel Hill North Carolina 27514 - February 11th, 2019
- Alumna to compete for Miss America crown on Sunday - UNCSA - February 3rd, 2019
- Stem Cell Therapy Latest Research Charlotte, North Carolina - December 2nd, 2018
- Stem Cell Therapy North Carolina | Regenerative Medicine ... - October 4th, 2018
- Bone Marrow Transplant | Durham, Raleigh, North Carolina ... - July 24th, 2018
- Charlotte, North Carolina - Stem Cells Transplant Institute - July 15th, 2018
- Stem Cell Greensboro North Carolina 27455 - July 15th, 2018
- Spotlights Archive | The University of North Carolina at ... - October 15th, 2017
- Stem Cells in Focus - Blog - Closer Look at Stem Cells - October 10th, 2017
- Avalon Advisors Has Decreased Its Comcast Cmn Class (CMCSA) Position; Neuralstem (CUR)'s Sentiment Is 0 - High Point Observer - September 6th, 2017
- Former basketball star Greg Friel in fight of his life - Fosters - Foster's Daily Democrat - August 15th, 2017
- Lung fibrosis? Stem cell therapy holds promise - The Hindu - The Hindu - August 11th, 2017
- Stem cells may treat lung fibrosis diseases - Futurity: Research News - August 11th, 2017
- CRISPR Edits Genome of Human Embryos - Alzforum - August 11th, 2017
- Cary NC Stem Cell Treatment | Cary North Carolina Cancer ... - November 16th, 2016
- Cato - Research Triangle Park, Durham, North Carolina - August 21st, 2016
- Biotechnology Teacher Resources Online | North Carolina ... - August 19th, 2016
- Stem Cell Research in North Carolina ... Whats Really ... - August 5th, 2016
- JCI - Type 2 alveolar cells are stem cells in adult lung - October 19th, 2015
- Cary North Carolina Stem Cell Research | Cary NC Stem Cell ... - July 2nd, 2015
- Core labs | North Carolina Biotech Center - April 29th, 2015
- Image: Human endothelial cells experiment bound for ISS - February 26th, 2015
- COPD Prognosis Stem Cells Canada, COPD Alternative ... - February 17th, 2015
- Cancer Care Northwest Stem Cell Transplantation - January 10th, 2015
- Dying child approved for new treatment testing - January 2nd, 2015
- New e-Incubator enables real-time imaging of bioengineered tissues in controlled unit - November 5th, 2014
- Committee on Development, Regeneration, and Stem Cell ... - October 31st, 2014
- Local doctor uses stem cells to heal - October 29th, 2014
- Study Offers Fertility Preservation Option to Young Boys with Cancer - October 1st, 2014
- Fayetteville North Carolina Stem Cell Research ... - September 16th, 2014
- Charlotte NC Resources - Stem Cells: Get Facts on Uses ... - September 1st, 2014
- For the first time, researchers isolate adult stem cells ... - August 26th, 2014
- The Man Who Grew Eyes From Scratch - August 26th, 2014
- Carolina Stem Cell Treatment Center | carolina stem ... - August 22nd, 2014
- North Carolina Stem Cell Treatment | Stem Cell Treatments - August 22nd, 2014