Immunofluorescence analysis of a group of proliferating stem cells associated with a muscle fiber (grey). The stem cells produce Dll1 (red) and MyoD (green). Two of the cells produce MyoG (blue): They are differentiating to form a new muscle cell. Note that the overlay of blue, green, and red appears as white. Credit: Birchmeier Lab, MDC
Three oscillating proteins cause new muscle cells to emerge from muscle stem cells in a balanced manner. In a paper being published in the journal Nature Communications, a team led by MDC researcher Carmen Birchmeier explains in detail how this process works.
When a muscle grows, because its owner is still growing too or has started exercising regularly, some of the stem cells in this muscle develop into new muscle cells. The same thing happens when an injured muscle starts to heal. At the same time, however, the muscle stem cells must produce further stem cells i.e., renew themselves as their supply would otherwise be depleted very quickly. This requires that the cells involved in muscle growth communicate with each other.
Two years ago, a team of researchers led by Professor Carmen Birchmeier, head of the Developmental Biology/Signal Transduction Lab at the Berlin-based Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC), showed that the development of stem cells into muscle cells is regulated with the help of two proteins, Hes1 and MyoD, which are produced in the progenitor cells in an oscillatory manner i.e., there are periodic fluctuations in the number of cells produced.
Both proteins are involved in the Notch signaling pathway, a widespread mechanism by which cells respond to external stimuli and communicate with other cells. The signaling pathway is named after its receptor Notch, onto which the ligand Delta, a cell surface protein, latches.
In our current study, we have provided unequivocal evidence that oscillation in muscle tissue is not just some strange phenomenon of the cells involved, but that these rhythmic fluctuations in gene expression are actually crucial for transforming stem cells into muscle cells in a balanced and controlled manner, says Birchmeier.
Together with researchers from Japan and France, Birchmeier and four other scientists at the MDC also uncovered the crucial role of a third protein that, along with Hes1 and MyoD, forms a dynamic network within the cells. As the team reports in the journal Nature Communications, this protein is the Notch ligand Delta-like1, or Dll1 for short. It is produced in activated muscle stem cells in a periodically fluctuating manner, with the oscillation period lasting two to three hours, Birchmeier explains, adding: Whenever a portion of the stem cells expresses more Dll1, the amount in the other cells is correspondingly lower. This rhythmic signaling determines whether a stem cell becomes a new stem cell or develops into a muscle cell.
In their experiments with isolated stem cells, individual muscle fibers and mice, Birchmeier and her teamfurther investigated how the Hes1 and MyoD proteins are involved in muscle growth. Put simply, Hes1 acts as the oscillatory pacemaker, while MyoD increases Dll1 expression, says Dr.Ines Lahmann, a scientist in Birchmeiers lab and a lead author of the study along with Yao Zhang from the same team.These findings were demonstrated not only in our experimental analyses, but also in the mathematical models created by Professor Jana Wolf and Dr.Katharina Baum at the MDC, Birchmeier says.
With the help of gene-modified mice, the researchers obtained the most important evidence that Dll1oscillation plays a critical role in regulating the transformation of stem cells into muscle cells. In these animals, a specific mutation in the Dll1 gene causes production of the protein to occur with a time delay of a few minutes, Birchmeier explains. This disrupts the oscillatory production of Dll1 in cell communities, but does not alter the overall amount of the ligand.
Nevertheless, the mutation has severe consequences on the stem cells, propelling them to prematurely differentiate into muscle cells and fibers, reports Zhang, who performed a large portion of the experiments. As a result, he says, the stem cells were depleted very quickly, which resulted, among other things, in an injured muscle in the mices hind legs regenerating poorly and remaining smaller than it had been before the injury. Quite obviously, this minimal genetic change manages to disrupt the successful communication in the form of oscillation between stem cells, Zhang says.
Only when Dll1 binds to the Notch receptor in an oscillatory manner and thus periodically initiates the signaling cascade in the stem cells is there a good equilibrium between self-renewal and differentiation in the cells, Birchmeier concludes. The MDC researcher hopes that a better understanding of muscle regeneration and growth may one day help create more effective treatments for muscle injuries and diseases.
Reference: Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells by Yao Zhang, Ines Lahmann, Katharina Baum, Hiromi Shimojo, Philippos Mourikis, Jana Wolf, Ryoichiro Kageyama and Carmen Birchmeier, 26 February 2021, Nature Communications.DOI: 10.1038/s41467-021-21631-4
See the original post:
Comments on: Scientists Uncover the Key to Proper Muscle Growth - SciTechDaily
- Chuck Chan, stem cell researcher who discovered how to regrow cartilage, dies at 48 - Palo Alto Online - May 4th, 2024
- Stem Cell and Platelet Rich Plasma Alopecia Therapies Market Analysis and Future Outlook by 2030 - openPR - May 4th, 2024
- Opinion: As stem cell biologists, we're concerned a Utah law will lead to a boom in snake oil sales - Salt Lake Tribune - May 2nd, 2024
- Robert Hariri: Developing Cost-Effective Cell Therapies From Placentas - BioSpace - May 2nd, 2024
- USC-led study introduces a new and improved way to grow the cells that give rise to the kidney's filtration system - EurekAlert - May 2nd, 2024
- Using stem cell-derived heart muscle cells to advance heart regenerative therapy - Medical Xpress - April 28th, 2024
- John Cleese is spending thousands on stem cell therapy is it really the secret to anti-ageing? - Yahoo Lifestyle Australia - April 28th, 2024
- SUM Hospital conducts Odishas first stem cell transplantation - The Times of India - April 24th, 2024
- Cancer treatment: What is stem cell therapy, and how does it work? - Moneycontrol - April 24th, 2024
- The murky, unregulated world of anti-ageing stem cell therapy - The Telegraph - April 24th, 2024
- Drug Prototype Promising in Treatment of Pulmonary Disease - Medscape - April 20th, 2024
- Man Paralyzed In Surfing Accident Regains Ability to Walk After Stem Cell Treatment - The Inertia - April 20th, 2024
- Medical breakthrough: 8-year-old boy first in New York to receive FDA-approved gene therapy for rare inherited blood disorder - WABC-TV - April 20th, 2024
- Stem Cell Treatment Helped A Man Who Was Paralyzed From The Neck Down To Stand On His Own - Bored Panda - April 20th, 2024
- UM, CUHK jointly hold symposium on stem cells and regenerative medicine - gcs.gov.mo - April 20th, 2024
- Paralysed patient now able to walk as stem cell therapy shows promising results - WION - April 15th, 2024
- Andrew Steele Sees Aging as the Root of Disease - Worth - Worth Magazine - April 15th, 2024
- The astonishing effect of stem cell implants - as groundbreaking treatment 'transforms' life for those with brain damage ... - Daily Mail - April 15th, 2024
- Consumer Alert on Regenerative Medicine Products Including Stem Cells - FDA.gov - April 13th, 2024
- This Startup Wants To Be OpenAI Of Stem Cell Therapy, Targets $250B Market - Forbes - April 13th, 2024
- Brain-cell transplants are the newest experimental epilepsy treatment - MIT Technology Review - April 3rd, 2024
- Global Regenerative Medicine Market to Touch Valuation of USD 472.95 Billion by 2032, at 25.86% CAGR: Astute ... - Yahoo Finance - April 1st, 2024
- Explosive Growth Projected for Stem Cell Market, Expected to Surpass $37 Billion by 2030 As Revealed In New... - WhaTech - April 1st, 2024
- Integrating New Therapies With Autologous Stem Cell Transplant in Myeloma - Targeted Oncology - April 1st, 2024
- New tool provides researchers with improved understanding of stem cell aging in the brain - Medical Xpress - March 30th, 2024
- The ISSCR announces 2024 election results - EurekAlert - March 28th, 2024
- Exosomes and Stem Cells Are the Future of Anti-Aging - NewBeauty Magazine - March 28th, 2024
- Charles River Extends Gene Therapy Alliance with NUS Medicine - Contract Pharma - March 22nd, 2024
- Exciting opportunities in stem cell technology and regenerative biology in Indian healthcare industry - Express Healthcare - March 22nd, 2024
- Charles River Announces Extension of Gene Therapy Manufacturing Alliance with NUS Yong Loo Lin School of Medicine - Yahoo Finance - March 22nd, 2024
- Opinion: The revolutionary sickle cell therapies - MSN - March 22nd, 2024
- 10 Years of Kansas Regenerative Medicine Center - KSAL - March 22nd, 2024
- BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership - Diagnostic and Interventional Cardiology - March 17th, 2024
- Cynata Therapeutics' breakthrough in regenerative medicine - Finance News Network - March 17th, 2024
- New Positive Data Presented on Briquilimab Conditioning in Patients with Fanconi Anemia - GlobeNewswire - March 17th, 2024
- Novel 3D stem cell therapy to treat critical limb ischaemia - Drug Target Review - March 15th, 2024
- Breaking Boundaries: Pharmicell's Bold Vision for Healthcare Transformation and Monumental Growth - The Worldfolio - March 15th, 2024
- CuSTOM Organoid Research Evolving From Tool to Treatment - Research Horizons - Research Horizons - March 15th, 2024
- BioCardia and StemCardia Announce Partnership to Deliver Cell-Gene Therapy for Remuscularization of Heart - Cath Lab Digest - March 15th, 2024
- Calidi Biotherapeutics and City of Hope Announce Funding from the California Institute for Regenerative Medicine ... - Business Wire - March 13th, 2024
- Iron restriction keeps blood stem cells young, researchers find - Phys.org - March 13th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 9th, 2024
- Trends in Stem Cell Transplantation Refusal for Myeloma Treatment - Targeted Oncology - March 7th, 2024
- Stem Cell Therapy Market (CAGR) of 31.1%, Future of Market Size Emerging Technologies and their Impact on ... - Taiwan News - March 7th, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 6th, 2024
- Advancing stem cell therapy: The regulatory process to get to clinical trials - The Economic Times - March 6th, 2024
- Transitioning from traditional surgical methods to the innovative use of stem cells - pharmaphorum - March 6th, 2024
- 'Mini organs' are grown from human stem cells taken during the late stages of pregnancy for the first time - m - Daily Mail - March 6th, 2024
- Stem cell transplant cures man of HIV and leukemia, one of five to achieve full remission - Fox 28 - March 3rd, 2024
- Stem Cell Therapy Market to Boost USD 137.5 Billion by 2034 and Projected to grow at 32.10% CAGR with increasing ... - Yahoo Finance - March 1st, 2024
- Studies expand use of stem cell therapies - WPLG Local 10 - March 1st, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Unlocking the Potential of Stem Cells: The Medical Revolution of the Century - EIN News - February 27th, 2024
- Pelage Pharmaceuticals Announces $16.75M Series A Financing led by GV to Revolutionize Regenerative Medicine ... - Yahoo Finance - February 27th, 2024
- Say Her Name - Henrietta Lacks, The Real Mother Of Stem - Her Campus - February 27th, 2024
- California Man Free of HIV And Cancer in Astonishing Medical Recovery - ScienceAlert - February 25th, 2024
- $93 million for research into improved health for children, young people and the aged, medical devices, mental health ... - Department of Health - February 25th, 2024
- Stem Cells in Regenerative Medicine - PMC - National Center for ... - February 24th, 2024
- The Promise and Reality of Stem Cell Therapy: What You Need to Know - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy: A Beacon of Hope for Patients with Untreatable Conditions - Corporate Wellness Magazine - February 22nd, 2024
- Leading Experts in Stem Cell Therapy: A Global Overview - Corporate Wellness Magazine - February 22nd, 2024
- Can Stem Cells Help Reverse the Effects of Aging? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cell Therapy for Cancer: Hope on the Horizon? - Corporate Wellness Magazine - February 22nd, 2024
- Stem Cells and Autism: A Closer Look at Innovative Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Regrowth and Restoration: The Science Behind Stem Cell Therapy for Hair - Corporate Wellness Magazine - February 22nd, 2024
- Brain Recovery: The Role of Stem Cells in Stroke and Cerebral Palsy Treatments - Corporate Wellness Magazine - February 22nd, 2024
- Turning Back the Clock: The Science of Stem Cells in Anti-Aging - Corporate Wellness Magazine - February 22nd, 2024
- Insights into cellular therapies for cancer treatment - Drug Target Review - February 22nd, 2024
- The Role of Stem Cells in Rheumatoid Arthritis Recovery - Corporate Wellness Magazine - February 22nd, 2024
- Dr Ernesto Romeros vision transforms immunotherapy regenerative medicine into a global leader in stem cell treatment - Khaleej Times - February 22nd, 2024
- World-Renowned Doctors Leading the Way in Stem Cell Research and Treatment - Medical Tourism Magazine - February 20th, 2024
- Choosing the Best: A Guide to America's Premier Stem Cell Therapy Providers - Medical Tourism Magazine - February 20th, 2024
- Navigating Through the Possibilities of Stem Cell Treatment for Eye Disorders - Medical Tourism Magazine - February 20th, 2024
- Global Leaders in Stem Cell Therapy: Where Excellence Meets Innovation - Medical Tourism Magazine - February 20th, 2024
- Excellence in Stem Cell Treatment: How the US is Pioneering Global Healthcare Solutions - Medical Tourism Magazine - February 20th, 2024
- Clarifying Memory Loss Treatments: The Role of Stem Cells - Medical Tourism Magazine - February 20th, 2024
- Battling Inflammation: Stem Cell Therapy for Rheumatoid Arthritis - Medical Tourism Magazine - February 20th, 2024
- Digestive Health and Stem Cells: Treating Ulcerative Colitis and Crohn's Disease - Medical Tourism Magazine - February 20th, 2024
- Top Stem Cell Clinics in the USA: Pioneering Treatments for Chronic Conditions - Medical Tourism Magazine - February 20th, 2024
- Stem Cells and Autism: Understanding the Potential for Innovative Treatments - Medical Tourism Magazine - February 20th, 2024
Recent Comments