Scientists pinpoint molecule that controls stem cell plasticity by boosting gene expression
By LizaAVILA
Stem cells can have a strong sense of identity. Taken out of their home in the hair follicle, for example, and grown in culture, these cells remain true to themselves. After waiting in limbo, these cultured cells become capable of regenerating follicles and other skin structures once transplanted back into skin. It's not clear just how these stem cells -- and others elsewhere in the body -- retain their ability to produce new tissue and heal wounds, even under extraordinary conditions.
New research at Rockefeller University has identified a protein, Sox9, that takes the lead in controlling stem cell plasticity. In a paper published Wednesday (March 18) in Nature, the team describes Sox9 as a "pioneer factor" that breaks ground for the activation of genes associated with stem cell identity in the hair follicle.
"We found that in the hair follicle, Sox9 lays the foundation for stem cell plasticity. First, Sox9 makes the genes needed by stem cells accessible, so they can become active. Then, Sox9 recruits other proteins that work together to give these "stemness" genes a boost, amplifying their expression," says study author Elaine Fuchs, Rebecca C. Lancefield Professor, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. "Without Sox9, this process never happens, and hair follicle stem cells cannot survive."
Sox9 is a type of protein called a transcription factor, which can act like a volume dial for genes. When a transcription factor binds to a segment of DNA known as an enhancer, it cranks up the activity of the associated gene. Recently, scientists identified a less common, but more powerful version: the super-enhancer. Super-enhancers are much longer pieces of DNA, and host large numbers of cell type-specific transcription factors that bind cooperatively. Super-enhancers also contain histones, DNA-packaging proteins, that harbor specific chemical groups -- epigenetic marks -- that make genes they are associated with accessible so they can be expressed.
Using an epigenetic mark associated specifically with the histones of enhancers, first author Rene Adam, a graduate student in the lab, and colleagues, identified 377 of these high-powered gene-amplifying regions in hair follicle stem cells. The majority of these super-enhancers were bound by at least five transcription factors, often including Sox9. Then, they compared the stem cell super-enhancers to those of short-lived stem cell progeny, which have begun to choose a fate, and so lost the plasticity of stem cells. These two types of cells shared only 32 percent of their super-enhancers, suggesting these regions played an important role in skin cell identity. By switching off super-enhancers associated with stem cell genes, these genes were silenced while new super-enhancers were being activated to turn on hair genes.
To better understand these dynamics, the researchers took a piece of a super-enhancer, called an epicenter, where all the stem cell transcription factors bind, and they linked it to a gene that glowed green whenever the transcription factors were present. In living mice, all the hair follicle stem cells glowed green, but surprisingly, the green gene turned off when the stem cells were taken from the follicle and placed in culture. When they put the cells back into living skin, the green glow returned.
Another clue came from experiments performed by Hanseul Yang, another student in the lab. By examining the new super-enhancers that were gained when the stem cells were cultured, they learned that these new super-enhancers bound transcription factors that were known to be activated during wound-repair. When they used one of these epicenters to drive the green gene, the green glow appeared in culture, but not in skin. When they wounded the skin, then the green glow switched on.
"We were learning that some super-enhancers are specifically activated in the stem cells within their native niche, while other super-enhancers specifically switch on during injury," explained Adam. "By shifting epicenters, you can shift from one cohort of transcription factors to another to adapt to different environments. But we still needed to determine what was controlling these shifts."
The culprit turned out to be Sox9, the only transcription factor expressed in both living tissue and culture. Further experiments confirmed Sox9's importance by showing, for example, that removing it spelled death for stem cells, while expressing it in the epidermis gave the skin cells features of hair follicle stem cells. These powers seemed to be special to Sox9, placing it atop the hierarchy of transcription factors in the stem cells. Sox9 is one of only a few pioneer factors known in biology that can initiate such dramatic changes in gene expression.
"Importantly, we link this pioneer factor to super-enhancer dynamics, giving these domains a 'one-two punch' in governing cell identity. In the case of stem cell plasticity, Sox9 appears to be the lead factor that activates the super-enhancers that amplify genes associated with stemness," Fuchs says. "These discoveries offer new insights into the way in which stem cells choose their fates and maintain plasticity while in transitional states, such as in culture or when repairing wounds."
Excerpt from:
Scientists pinpoint molecule that controls stem cell plasticity by boosting gene expression
- Jessner's Lymphocytic Infiltration of the Skin Mimicking Rosacea: A Rare Case Presentation - Dermatology Times - April 28th, 2024
- Device improves stem cell generation and chance for accessible Alzheimer's cell therapy | KTH Royal Institute of ... - TT Nyhetsbyrn - April 28th, 2024
- Colossal Creates Elephant Stem Cells for the First Time in Quest to Revive the Woolly Mammoth - Singularity Hub - March 18th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 10th, 2024
- A dive into the genetic history of India, and the role of vitamin A in skin repair - Science - March 10th, 2024
- Herbosa: Clinic under probe after skin treatments linked to womans death - Philstar.com - January 22nd, 2024
- These Will Be the Biggest Skin-Care Trends of 2024 - Allure - December 28th, 2023
- Sorry, But These 10 Skincare Products Are A Scam - Refinery29 - December 12th, 2023
- Cyclerion Strengthens Board of Directors with Experienced Company Builder and Cutting-edge Innovator - December 4th, 2023
- Aptose Appoints Fletcher Payne Chief Business Officer, Expanding his Executive Role - December 4th, 2023
- Opthea to Present at the FLORetina 2023 Congress - December 4th, 2023
- HUTCHMED Highlights Clinical Data to be Presented at 2023 ESMO Asia and ESMO Immuno-Oncology Congresses - December 4th, 2023
- AC Immune Strengthens Management, Appoints Madiha Derouazi as CSO and Christopher Roberts as CFO - December 4th, 2023
- Publication of a transparency notification received from Tolefi SA (Article 14 §1 of the Law of 2 May 2007) - December 4th, 2023
- Annovis Bio Appoints Andrew Walsh as Vice President Finance - December 4th, 2023
- Foghorn Therapeutics Announces Clinical Data from Phase 1 Study of FHD-286, a Novel BRG1/BRM Inhibitor, in Patients with Advanced Hematologic... - December 4th, 2023
- Akari Therapeutics Appoints Experienced Life Sciences Entrepreneur Samir R. Patel, M.D. to Board of Directors - December 4th, 2023
- Ovid Therapeutics to Present Five Abstracts Supporting its Epilepsy Programs at the 77th American Epilepsy Society Annual Meeting (2023) - December 4th, 2023
- Spectral Medical Announces CFO Departure - December 4th, 2023
- Are STEM CELL EXOSOMES the secret to a 'snatched' jawline? Discover the products that influencers are claiming - Daily Mail - November 18th, 2023
- Defence Mechanisms: Four ways your body is protecting you every time you fall sick - indulgexpress - May 16th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, 111SKIN, Nest & More - E! NEWS - May 16th, 2023
- INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - April 5th, 2023
- Skin Regeneration: The Science and How to Boost It - Healthline - March 9th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, U Beauty, Nest & More - E! NEWS - March 1st, 2023
- 7-year-old vows to find a cure for brother in need of bone marrow transplant - WJLA - February 21st, 2023
- World's most radioactive man 'cried blood' as his skin melted in 83-day nightmare - Times Now - February 4th, 2023
- How old are you, really? The answer is written on your face. - National Geographic UK - February 4th, 2023
- Skin: Layers, Structure and Function - Cleveland Clinic - January 27th, 2023
- Human skin | Definition, Layers, Types, & Facts | Britannica - January 27th, 2023
- Skin Disorders: Pictures, Causes, Symptoms, and Treatment - Healthline - January 27th, 2023
- Skin care: 5 tips for healthy skin - Mayo Clinic - January 27th, 2023
- Skin Care and Aging | National Institute on Aging - January 27th, 2023
- Wrinkles - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Dry skin - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Stem cells: a brief history and outlook - Science in the News - January 3rd, 2023
- Still Drinking Green Tea? Doctor Reveals A Healthier Drink With Proven Benefits For Diabetes, Aging, Oxidative Stress, And Cancer - Revyuh - January 3rd, 2023
- RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells - India Education Diary - December 25th, 2022
- The Use of Stem Cells in Burn Wound Healing: A Review - Hindawi - December 1st, 2022
- FACTORFIVE Skincare The Power of Stem Cells for Skin - December 1st, 2022
- Embryonic Stem Cells - The Definitive Guide | Biology Dictionary - December 1st, 2022
- From pro soccer hopeful to hip hop artist with illness and addiction along the way, Tymaz Bagbani releases debut album - Toronto Star - December 1st, 2022
- Stem Cells | The ALS Association - November 22nd, 2022
- What is a stem cell? YourGenome - October 29th, 2022
- Skin Cell - The Definitive Guide | Biology Dictionary - October 29th, 2022
- Explora Journeys Plans Extensive Fitness And Well-Being Initiatives At Sea, Right On Trend - Forbes - October 29th, 2022
- Ahead of the holiday shopping season, Amazon kicks off second annual Holiday Beauty Haul on Oct. 24 - KXAN.com - October 21st, 2022
- Human skin color - Wikipedia - October 13th, 2022
- Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies - October 13th, 2022
- Skin Grafting, Cryopreservation, and Diseases: A Review Article - Cureus - October 13th, 2022
- Anti-ageing cosmetics: Can they turn back the hands of the clock? - The Sunday Guardian Live - The Sunday Guardian - October 13th, 2022
- Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry - Yale News - October 13th, 2022
- The Switch to Regenerative Medicine - Dermatology Times - October 13th, 2022
- Last Chance to Get The Collagen-Infused Massage Oil That Moisturizes Skin & Diminishes Cellulite For Less Than $20 - msnNOW - October 13th, 2022
- Addison's Disease Explained: Causes, Symptoms, And Treatments - Health Digest - October 13th, 2022
- Stem Cells Therapy for Autism: Does it Work? - October 5th, 2022
- Stem-like CD8 T cells mediate response of adoptive cell ... - PubMed - October 5th, 2022
- 6 Under Eye Products You Need To Have STAT - Grazia India - October 5th, 2022
- CellResearch Corporation (CRC) to present promising new stem cell products for the treatment of chronic diabetic foot ulcers at the world's premier... - September 27th, 2022
- Reprogramming pig cells leads way for new regenerative therapies - National Hog Farmer - September 27th, 2022
- A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights - The Financial Express - September 27th, 2022
- Tajmeel redefines beauty to give its patients the best results - Gulf News - September 27th, 2022
- Here Is Why You Heal Slower As You Age - Health Digest - September 27th, 2022
- Creating stem cells from minipigs offers promise for improved treatments - University of Wisconsin-Madison - September 19th, 2022
- Israeli Biotech Firm Plans to Create Human Embryos to Harvest Organs, Field Experts Say There are Ethical Concerns - CBN.com - September 19th, 2022
- CellResearch Corporation (CRC) announces positive results of Phase I study for CorLiCyte - PR Newswire - September 19th, 2022
- The best CBD and hemp products for pampering your skin this fall - Leafly - September 19th, 2022
- Benjamin Button For Real? Scientists Are Close To Cracking The Code To Reverse Aging - Worldcrunch - September 19th, 2022
- I took an international trip with my frozen eggs to learn about the fertility industry - MIT Technology Review - September 19th, 2022
- Propanc Biopharma Reports Significant Effects of PRP Against the Tumor Microenvironment - Business Wire - September 11th, 2022
- 6 Ingredients to Avoid Putting on Your Skin - Healthline - September 3rd, 2022
- Regenerative Properties of the Newborn Heart Offers Hope for Those With Congenital Heart Disease - The Epoch Times - September 3rd, 2022
- Meet White Orange: The Vitamin C Skin Care Brand For Sensitive Skin - Bustle - September 3rd, 2022
- Rejuvenation Roundup August 2022 - Lifespan.io News - September 3rd, 2022
- To better understand Parkinson's disease, this San Diego expert sent her own cells to space - The San Diego Union-Tribune - August 26th, 2022
- Inside the race to make human sex cells in the lab - MIT Technology Review - August 26th, 2022
- Global Biomaterials Market to Reach Value of $372.7 Billion by 2028 | Demand For Biomaterials in the Healthcare Industry will Grow by 53% Over the... - August 26th, 2022
- A Groovy Guide to Anti-Aging Products With CBD and Mushrooms - Out Magazine - August 26th, 2022
- New milestone organoid synthesis will boost disease and drug development research - RegMedNet - August 10th, 2022
- Victoria Beckham and Kim Kardashian are fans of Augustinus Baders skincare range - and you can get 20% off - The Mirror - August 10th, 2022