Translucently colored embryonic stem (ES) cell (upper right) and its differentiating derivatives (left and lower right). The small round bodies inside cells represent lysosomes, with the pink color indicating ones that are undergoing chaperone-mediated autophagy (CMA), a selective form of autophagy that is demonstrated only in mammals. CMA governs the balance between self-renewal and differentiation of ES cells. It is kept at low levels in undifferentiated ES cells to maintain the pluripotent state. Upon induction of differentiation, CMA flux increases due to the reduction of pluripotency factors, leading to changes in cellular metabolism and epigenetic landscape that favor differentiation.
PHILADELPHIAThe self-eating process in embryonic stem cells known as chaperone-mediated autophagy (CMA) and a related metabolite may serve as promising new therapeutic targets to repair or regenerate damaged cells and organs, Penn Medicine researchers show in a new study published online in Science.
Human bodies contain over 200 different types of specialized cells. All of them can be derived from embryonic stem (ES) cells, which relentlessly self-renew while retaining the ability to differentiate into any cell type in adult animals, a state known as pluripotency. Researchers have known that the cells metabolism plays a role in this process; however, it wasnt clear exactly how the cells internal wiring works to keep that state and ultimately decide stem cell fate.
The new preclinical study, for the first time, shows how the stem cells keeps CMA at low levels to promote that self-renewal, and when the stem cell is ready, it switches that suppression off to enhance CMA, among other activities, and differentiate into specialized cells.
Its an intriguing discovery in the field of stem cell biology and for researchers looking to develop therapies for tissue or organ regeneration, said senior author Xiaolu Yang, PhD, a professor of Cancer Biology at the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania. We reveal two novel ways to potentially manipulate the self-renewal and differentiation of stem cells: CMA and a metabolite, known as alpha-ketoglutarate, that is regulated by CMA. Rationally intervening or guiding these functions could be a powerful way to increase the efficiency of regenerative medicine approaches.
Autophagy is a cell-eating mechanism necessary for survival and function of most living organisms. When cells self-eat, the intracellular materials are delivered to lysosomes, which are organelles that help break down these materials. There are a few forms of autophagy. However, unlike the other forms, which are present in all eukaryotic cells, CMA is unique to mammals. To date, the physiological role of CMA remains unclear.
Using metabolomic and genetic laboratory techniques on the embryonic stem cells of mice, the researchers sought to better understand significant changes that took place during their pluripotent state and subsequent differentiation.
They found that CMA activity is kept at a minimum due to two cellular factors critical for pluripotencyOct4 and Sox2that suppresses a gene known as LAMP2A, which provides instructions for making a protein called lysosomal associated membrane protein-2 necessary in CMA. The minimal CMA activity allows stem cells to maintain high levels of alpha-ketoglutarate, a metabolite that is crucial to reinforce a cells pluripotent state, the researchers found.
When its time for differentiation, the cells begin to upregulate CMA due to the reduction in Oct4 and Sox2. Augmented CMA activity leads to the degradation of key enzymes responsible for the production of alpha-ketoglutarate. This leads to a reduction in alpha-ketoglutarate levels as well as an increases in other cellular activities to promote differentiation. These findings reveal that CMA and alpha-ketoglutarate dictate the fate of embryonic stem cells.
Embryonic stem cells are often called pluripotent due to their remarkable ability to give rise to every cell type in the body, except the placenta and umbilical cord. Embryonic stem cells not only provide a superb system to study early mammalian development, but also hold great promise for regenerative therapies to treat various human disorders. The development of stem-cell based regenerative medicine therapies has rapidly increased in the last decade, with several approaches in studies shown to repair damaged heart tissue, replace cells in solid organ transplantation, and in some cases address neurological disorders.
This newly discovered role of autophagy in the stem cell is the beginning of further investigations that could lead to researchers and physician-scientists to better therapies to treat various disorders, Yang said.
Penn co-authors of the study include the first author Yi Xu, a post-doctoral researcher in Yangs Lab, Yang Zhang and Sixiang Yu, also in Yangs lab, Lili Guo and Ian A. Blair of the department of Systems Pharmacology and Translational Therapeutics, Mengyuan Kan of the department of Biostatistics, Epidemiology and Informatics, as well as Juan C. Garca-Caaveras and Joshua D. Rabinowitz of Princeton University.
The study was supported the National Institutes of Health (R01CA182675, R01CA184867, R01CA235760, and P30ES013508, and the Department of Defense (W81XWH-15-1-0678).
- Global Human Embryonic Stem Cells Market 2020 to Witness Huge Growth by 2026 | Top Key Players; Lonza Group Ltd., Life Technologies Corporation,... - September 28th, 2020
- Stem Cell Market Potential Growth, Size, Share, Demand and Analysis of Key Players Research Forecasts to 2027 - The Daily Chronicle - September 28th, 2020
- Hair loss treatment: Breakthrough research links one ingredient to hair growth - Express - September 28th, 2020
- Cell Freezing Media for Cell Therapy Market To Witness Growth Acceleration Duri - News by aeresearch - September 28th, 2020
- Stem Cell Characterization and Analysis Tool Market Share, Sales Channels and Overview Till 2025 - The Research Process - September 26th, 2020
- Human Embryonic Stem Cells (HESC) Market is Expected to Witness Significant Growth-Says QYResearch | , ESI BIO, Thermo Fisher, BioTime, MilliporeSigma... - September 20th, 2020
- Species-specific pace of development is associated with differences in protein stability - Science Magazine - September 20th, 2020
- The Fascinating Story of Q Stock BioRestorative Therapies Inc (OTCMKTS: BRTXQ) - MicroCap Daily - September 20th, 2020
- Global Stem Cell Therapy Market 2020 Research on Import-Export Details, Business Standards and Forecast to 2025 - Scientect - September 16th, 2020
- Insights Into the Structure and Function of the Immortality Protein - Technology Networks - September 15th, 2020
- Global Cell Freezing Media for Cell Therapy Industry Report 2020 History, Present and Future - Express Journal - September 15th, 2020
- Patenting Stem Cell Inventions in India- What to Expect? - Lexology - September 11th, 2020
- Stem Cell Banking Market will Hit Big Revenues in Future | COVID19 Unlock opportunities - The Daily Chronicle - September 11th, 2020
- Novel discovery could lead to stem cell-based treatment for heart failure - News-Medical.Net - September 11th, 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
- Global Stem Cell Reconstructive Market- Industry Analysis and Forecast (2020-2027) - Kewaskum Statesman News Journal - September 11th, 2020
- Development Trends and Financial Analysis of Stem Cell Assay Market - The Daily Chronicle - September 11th, 2020
- School of Science grows by 10 - MIT News - September 8th, 2020
- Stem Cell Therapy Market to Fuel Revenues Through 2020 Lake Shore Gazette - Lake Shore Gazette - September 8th, 2020
- Kerala's KK Shailaja tops as women dominate top 10 of Prospect's 'thinkers for the COVID-19 age' list - The New Indian Express - September 8th, 2020
- Cell Therapy Manufacturing Market to be Worth USD 8 billion by 2030, predicts Roots Analysis - Scientect - September 8th, 2020
- Live-cell imaging and analysis reveal cell phenotypic transition dynamics inherently missing in snapshot data - Science Advances - September 8th, 2020
- An ancient virus might have made our hearts bigger - Scope - Scope - September 8th, 2020
- How Groups of Cells Cooperate to Build Organs and Organisms - The Scientist - September 3rd, 2020
- Study reveals genetic mutations may be linked to infertility, early menopause - Sify News - September 3rd, 2020
- Scientists create embryonic stem cells without destroying ... - August 29th, 2020
- Practical Problems with Embryonic Stem Cells | USCCB - August 29th, 2020
- Foetal cells are used to make the Oxford coronavirus vaccine. But they came from a foetus in 1973 - ABC News - August 29th, 2020
- Global Stem Cell Reconstructive Market- Industry Analysis and Forecast (2020-2027) - Galus Australis - August 29th, 2020
- Translational Regenerative Medicines Market: Which Region Will Register Higher CAGR? 2017-2026 - Scientect - August 29th, 2020
- Stem Cell Therapy Market: Trends, Applications, Industry Competitive Analysis, Growth,Forecast: 2019 to 2029 - The Scarlet - August 29th, 2020
- Cellular Reprogramming Tools Market 2020 (Covid-19 Impact) In-depth Industry Analysis By Types, Applications and Forecast 2026: Celgene, Cynata,... - August 27th, 2020
- Pro-life groups applaud Trump administration advisory board for rejecting fetal tissue research proposals - Christianity Daily - August 27th, 2020
- Global regenerative medicine market size was USD 23841.5 Million in 2018 and is Projected to Reach USD 151949.5 Million by 2026, Exhibiting a CAGR of... - August 27th, 2020
- Archbishops vaccine stance out of tune with community - The Age - August 27th, 2020
- Cellular Reprogramming Tools Market- By Type, Component, Industry, Region Market Size, Demand Forecasts, Company Profiles, Industry Trends and... - August 22nd, 2020
- Stem Cell Therapy Market by Treatment,Application,End Users and Geography Forecast To 2026 - Good Night, Good Hockey - August 22nd, 2020
- Global Stem Cells Market Report Forecast to 2025 by Global Market Insights, Key Companies and Driving Trends| CCBC, Vcanbio, Boyalife, Beikebiotech -... - August 20th, 2020
- Ron Evans steals a trick from I/O, and points the way to a transformational diabetes therapy - Endpoints News - August 20th, 2020
- AgeX Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business Update - Stockhouse - August 20th, 2020
- Stem Cell Therapy Market Landscape Assessment By Type and Analysis Current Trends by Forecast To 2025 - The Daily Chronicle - August 19th, 2020
- Stem Cell Therapy Market Size By Product Analysis, By Application, By End-Users, By Regional Outlook, By Top Companies and Forecast to 2027 - Bulletin... - August 19th, 2020
- Stem Cell Therapy Market Size and Growth By Leading Vendors, By Types and Application, By End Users and Forecast to 2027 - Bulletin Line - August 19th, 2020
- ASU engineers get to the heart of organs-on-a-chip - ASU Now - August 19th, 2020
- Cell Isolation/Cell Separation Market Research Report by Product, by Cell Type, by Cell Source, by Technique, by Application, by End User - Global... - August 16th, 2020
- What Are the Five Warning Signs of Testicular Cancer? - MedicineNet - August 16th, 2020
- Stem Cell Banking Market Industry Analysis & Forecast (2019-2026) by Type, Service, Application and Geography. - Good Night, Good Hockey - August 13th, 2020
- Human Embryonic Stem Cells market to see major growth by 2026 | Lonza Group Ltd., Life Technologies Corporation, NuVasive Inc., TiGenix NV, Sumanas,... - August 11th, 2020
- New Study Presents Cell-based Therapy for MN Diseases or Spinal Cord Disorders - Mirage News - August 11th, 2020
- How Close Are We To Making Babies from Bone Marrow? - Discover Magazine - August 11th, 2020
- H.C. Wainwright Keeps Their Buy Rating on Lineage Cell Therapeutics (LCTX) - Smarter Analyst - August 7th, 2020
- Global Stem Cell Reconstructive Market- Industry Analysis and Forecast (2020-2027)-by Sources, Cell Type, Application, End User and Region. - WOLE TV - August 5th, 2020
- The Trouble With CRISPR The Strand - Strand - August 5th, 2020
- Global Stem Cell Reconstructive Market- Industry Analysis and Forecast (2020-2027)-by Sources, Cell Type, Application, End User and Region. - Red... - July 30th, 2020
- Human Embryonic Stem Cells (HESC) Market Growth by Top Companies, Trends by Types and Application, Forecast to 2026|ESI BIO, Thermo Fisher, BioTime -... - July 30th, 2020
- Waveguide Combiners & Dividers Market 2020 Global Share, Growth, Size, Opportunities, Trends, Regional Overview, Leading Company Analysis, And Key... - July 30th, 2020
- Expanded encyclopaedias of DNA elements in the human and mouse genomes - Nature.com - July 30th, 2020
- Global Stem Cell Therapy Market 2020 Analysis by Geographical Regions, Type and Application Till 2027 - Market Research Posts - July 30th, 2020
- New model may explain why certain cancer cells are resistant to therapy - News-Medical.Net - July 30th, 2020
- Stem Cell Characterization and Analysis Tool Market 2020 Report Forecast By Global Industry Trends, Future Growth, Regional Overview - Express Journal - July 28th, 2020
- Researchers Discover a New Side of Cancer that May Explain Its Resistance to Treatment - Genetic Engineering & Biotechnology News - July 28th, 2020
- Letters to editor: Sundial Bridge gathering, Donald Trump and COVID-19 - Record Searchlight - July 28th, 2020
- Stem Cell Therapy Market to Surpass US$ 40.3 Billion by 2027, Owing to Increasing Incidence of Spina - PharmiWeb.com - July 24th, 2020
- 'Embryoids' not the breakthrough they're made out to be - The B.C. Catholic - July 24th, 2020
- Genetic puzzle: How mice can be modified to help in the race to develop coronavirus therapies - Genetic Literacy Project - July 24th, 2020
- What's next for Tony Fauci, if the White House continues to sour on him? - STAT - July 16th, 2020
- Stem Cell Characterization and Analysis Tool Market 2020-2026 | Comprehensive Study of COVID-19 Impact | Worldwide Key Players: Osiris Therapeutics,... - July 14th, 2020
- Turning off junk DNA may free stem cells to become neurons - National Institutes of Health - July 14th, 2020
- Why are scientists trying to manufacture organs in space? - Space.com - July 14th, 2020
- Stem Cell Characterization and Analysis Tool Market Growth, Size, Opportunities and Analysis Forecast 2020 - 3rd Watch News - July 14th, 2020
- What Miniature Lab-Grown Brains Reveal About the Effects of Covid-19 - OneZero - July 14th, 2020
- Transdermal Testosterone Market Size By Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies And Forecast Up To 2026 -... - July 14th, 2020
- Impact Analysis of COVID-19 on Stem Cells Market Study 2018-2028 Segmented On The Basis of Product Type, Geographical Analysis, Future Forecast,... - July 11th, 2020
- COVID-19 Impact and Recovery Analysis on Cell Freezing Media for Cell Therapy Market 2020-2026 by BioLife Solutions, Akron Biotechnology, GE... - July 11th, 2020
- Stem Cell Therapy Market : Global Forecast over 2025 Cole of Duty - Cole of Duty - July 10th, 2020
- Stem Cells Market Emerging Trends, Business Opportunities, Segmentation, Production Values, Supply-Demand, Brand Shares and Forecast 2020-2027 - Cole... - July 10th, 2020
- Human Embryonic Stem Cells (HESC) Market Growth By Manufacturers, Type And Application, Forecast To 2026 - 3rd Watch News - July 10th, 2020
- Human CNS barrier-forming organoids with cerebrospinal fluid production - Science Magazine - July 10th, 2020
- Why we still haven't cloned humans it's not just ethics - Business Insider - Business Insider - July 10th, 2020
- Network Traffic Analyzer Market Size 2020 Global Industry Insights, Share, Growth, Trend, Demand, Top Players, Opportunities and Forecast to 2025 -... - July 10th, 2020