Powered by Blogger.

MicroRNA and stem cells II

Saturday, August 16, 2008

MicroRNA and stem cells are both pretty hot topics these days. But curiously, there haven't been a whole lot of reports that involve the two together. My last discussion of both, back in March, is here.

However, the combination of microRNA and stem cells just was back in the news, as briefly noted here.

As you recall, microRNA refers to small single-stranded RNA molecules, generally about 21 to 23 nucleotides in length. Each different microRNA (miRNA for short) is transcribed from a DNA gene like any other gene, but the resulting RNA isn't translated into a protein. Instead, the typical miRNA functions by downregulating the expression of another gene that codes for a protein.

An embryonic stem cell (ESC) has the property of pluripotency, which means that it is capable of giving rise to essentially any type of cell in the body of a multicellular organism. Whenever an ESC divides, the resulting daughter cells may also by ESCs (hence pluripotent) or they may be more specialized cells that will eventually give rise to some type of adult body cell.

In any particular ESC, the determination of remaining pluripotent or instead heading down the path to a more specialized cell type depends on what set of genes are expressed. Since miRNAs downregulate gene expression, they can keep an ESC in its pluripotent state, if they are active and suppress a gene that would make an ESC more specialized. But then if such a miRNA is blocked from being expressed, the ESC can start to become more specialized.

On the other hand, as we shall see, some miRNAs may block transcription factors that are needed to maintain a pluripotent state. Such an miRNA needs to be silent in an ESC, so some other protein needs to suppress its expression. (The miRNA called miR-21, discussed later, is an example.)

So the name of the game in studying ESCs, as far as miRNA is concerned, is to figure out what causes a miRNA gene to be expressed or not. Like other genes in an ESC, which genes are expressed is strongly controlled by a few master transcription factors.

There are four such transcription factors which seem to be especially important in ESCs: Oct4, Sox2, Nanog, and Tcf3. As discussed here, the first three of these factors have been found capable of playing a role in turning an ordinary adult cell into a pluripotent stem cell (called an "induced pluripotent stem cell").

Currently there are 336 mature mouse miRNAs known, and 441 mature human miRNAs. It is simple (given the known, complete sequences of mouse and human genomes) to locate the genes for each miRNA. However, in order to determine when a transcription factor regulates the miRNA gene, the promoter for the gene (a separate portion of DNA) must also be located. In order for a gene to be expressed, the right transcription factors have to bind to the gene's promoter.

Finding promoters is a lot harder, but there are techniques that involve searching for methylation of histone proteins that make up the nucleosomes around which cellular DNA is wrapped.

It was known, before the recent research we're discussing, that there were 14,230 sites in the genome where all four of the named master transcription factors could bind simultaneously. Most of those sites were not promoters of some miRNA, but it was straightforward to identify those that were. Of those miRNAs that appeared to be regulated by Oct4, Sox2, Nanog, and Tcf3, it was found that most are in fact preferentially expressed in ESCs. This set of miRNAs would seem to be good candidates for maintaining ESC pluripotency by downregulating other genes.

On the other hand, some of the miRNAs mediated by the transcription factors are silent in ESCs. Subsequent research found that another type of proteins (polycomb proteins) also bind to the miRNA promoters. These proteins were already known to block transcription by binding to gene promoters. But it turns out that some of these silenced miRNAs become active once the ESC loses its pluripotency and begins to differentiate.

The next step will be to figure out what each of these miRNAs regulated by Oct4, Sox2, Nanog, and Tcf3 actually does – either in the ESC or a differentiated cell. That should be very interesting, as the press release suggests:

Putting microRNAs on the stem cell map (8/7/08)
“We now have a list of what microRNAs are important in embryonic stem cells,” says Alex Marson, co-lead author on the paper and an MD/PhD student in the Young lab. “This gives us clues of which microRNAs you might want to target to direct an embryonic stem cell into another type of cell. For example, you might be able to harness a microRNA to help drive an embryonic stem cell to become a neuron, aiding with neurodegenerative disease or spinal cord injury.”

Moreover, the results give scientists a better platform for analyzing microRNA gene expression in cancer and other diseases. “We and others are finding that the overall gene circuitry for embryonic stem cells and cancer cells is very similar,” notes Marson. “Now that we have connected the circuitry to microRNAs, we can begin to compare microRNAs that are regulated in embryonic stem cells to those in cancer cells.”

Here's a somewhat more detailed description of the research: Stem Cell microRNA, Transcription Factor Interplay Uncovered (8/8/08)

Other research on miRNA and ESCs that has appeared since the previous discussion (here) gives a small taste of what may be learned about the miRNAs silenced in ESCs:

Protein Protects Embryonic Stem Cells' Versatility And Self-renewal (3/23/08)
A protein known as REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves and causes them to differentiate into specific cell types, scientists at The University of Texas M. D. Anderson Cancer Center report in the journal Nature.

Researchers show RE1-silencing transcription factor (REST) plays a dual role in embryonic stem cells, said senior author Sadhan Majumder, Ph.D., professor in M. D. Anderson's Department of Cancer Genetics. "It maintains self-renewal, or the cell's ability to make more and more cells of its own type, and it maintains pluripotency, meaning that the cells have the potential to become any type of cell in the body."

The details are particularly interesting:
In studies using mouse embryonic stem cells, the researchers found that REST disarms a specific microRNA called microRNA-21 or miR-21. MicroRNAs are tiny pieces of RNA that control gene expression by binding to the gene's messenger RNA.

The team found that MiR-21 suppresses embryonic stem cell self-renewal and is associated with a corresponding loss of expression of critical self-renewal regulators, such as Oct4, Nanog, Sox2 and c-Myc. REST counters this by suppressing miR-21 to preserve the cells' self-renewal and pluripotency.

The researchers discovered the roles of REST and miR-21 in a series of experiments using cultured mouse embryonic stem cells in either a self-renewal state or a differentiating state. They found that REST expression was significantly higher in the self-renewal state. Withdrawing REST reduced the stem cells' ability to reproduce themselves and started differentiation -- even when the cells were grown under conditions conducive to self-renewal. Adding REST to differentiating cells maintained their self-renewal.

These experiments also revealed that REST is bound to the gene chromatin of a set of microRNAs with the potential to target self-renewal genes. REST controls transcription of 11 microRNAs.

Is anything special known about miR-21? Yes, in fact – it is known to play a role in cancers of the colon, liver, and thyroid. (See here.)

Tags: , ,

No comments:

Post a Comment

 

Knowledge Link Suggest

Drug Abuse Online Lottery Games Drug Abuse Health and Fitness Health and Fitness free music downloads Law Reports Wallpapers Artist online shop originals Product Auto Parts Web Developer online shop originals Product Insurance Company Health Life Technology System Home Security Beauty Cosmetic Online Travel Agency Linux Tips Guide Shooting Simulator Gadgets Technology Project Build Houses Payday Loans Health News Information Animals Shop Travel Agency North Owl Network Dentist Healthy Aging asian pretty The Tool Hospital Barbecook Best way to make Money with Forex Trading Green Home Design Online Lottery atozbythesea.eu.org augmentezvosventes.eu.org automobielbedrijf.eu.org aworldofwindows.eu.org aws-orgware.eu.org azregionalmls.eu.org bacimamma.eu.org Business Plan Competition travel channel and rental cars Pharmacy and drugs Criminal Justice Planning Agency Lawyers Association The Best of Insurance http://celebritytidings.eu.org http://livingandfashion.eu.org Academic Advising Audio logo Stock Audio auto repair advice guide Healthy Women Medical Centre busy with business Car Finance Tools Debt Settlement Lawyer crafty stash corner cuentas and colors Cheap Wedding Dresses drug abuse statistics Lifestyle Home Solutions education essay titles finance insurance premium Lawyer and Legal Information guide healthy recipes health problems of children health topics kids home decorating service home improvement project home improvement project management home improvement project planning home insurance morgages house insurance plan house insurance progressive The Savings Bank insurance agency business loans insurance business loans insurance premium loan legacy landscape blocks legacy landscape contractors legacy landscape materials personal insurance loan real estate for commercial Bedroom Furniture Lawyer Requirements Concept Design teach about alcohol abuse technology support autocar the family deal tile flooring ideas tips lifetime fitness tips reduce car insurance quotes Online Jewelry Stores traveller hotel Insurance and Finance Auto and Parts wood flooring ideas the networks board game Adult Learning Theories sexy lingerie tattoo designs wallpaper artist health category insurance financial category Category Online Money Category Home Improvement online business category Category software games and android category marketing advertising category marketing advertising Home Solution Real Estate Financing Lucepedia Sports and Fitness Train Now Business Economy Global auto car loans car loans insurance Health Information how to prevent diabetes Best Credit Cards Cheap Wedding Dresses Small Business Finance Systems Body Health Home Improvement Services Guide Android Apps and Games fashion design Alcoholism Android Phones Board Games Cheap Tickets and Vacation Packages Online Prevent Child Obesity Prevent Premature Ejaculation Labor Lawyers Home Interior Design Ideas plumbers and carpet cleaning service diet and slimming Beautiful Picture Doctors Dental Care music video art BurningPedia Guide Planning Home Improvement Beauty Cosmetic Web Development Company lawyer requirements Books On Children Education security innovation work iPhone and iPad Turkey The Medical School Barbecue Electric The Linux Documentation Project Mental Health Care New Car Buying Guide House Curtains Dentist All System Education iPhone Specifications Cloud Trading Strategy mortgages and loans Pharmaceutical Info Online Application Service Provider The Masterchef Business Service Delivery Arts and Entertainment Pokerstars Real Money The Masterchef Electric Motors Gadgets Technology Casino Zone Small Business Solutions Home Advice Fashion Design Clothing Adventure Games Health and Fitness Hospital Equipment Plan Life Insurance public transportation services Prevent Premature Ejaculation Best Professional Carpet Cleaning Web Hosting Vehicle Emissions Inspection Drug Abuse Collection Travel Agency Medical Herbs color vision casting Aromatherapy Tips community film Cardio Tips Top Best Home Improvements Article Marketing Colon Cleanse Tips Terms and Conditions of Sale Products for Treating Acne Scars Natural Beauty Products Seo Web Marketing Business Prospects Trade Online Tool House Cleaner Bathing Equipment Financial Solutions Credit Loans Business Insurance Best Supplements Online Affiliate Marketing Web Design Jobs Online Business Degrees Travel and Leisure Hotel Business Online Payment Processor Women Management Criminal Law Marketing Product Webdesign Transportation Services The Marketing Business Prospects Trade Online Shop bed furniture free movies online Direct Hardware Supply Free Download PDF Technology Ipad doctors Specials Medical Dictionary Legacy Landscape Bank South Pacific Carpet Cleaner Best Internet Business Seo Web Marketing Doctor Healthy Doctors Diet Program Health Benefits of Drinking Water ups pills drugs Best Supplements dynasty fine jewelry Ceramic Floor Tile Online Business Degrees Property Residential and Commercial Real Estate All About Medical Bankruptcy Prevent Child Obesity Handbag and Shoes Education of Children physiotherapy school Cheap Airline Tickets Healthy Life PET online Interzoo Rehabilitation Center electric hybrid vehicles Baidu Software Center Automotive Advertising Agencies Health and Care Virtual private network Student Education Technosound Wedding Dresses excel archives Classic Car Restoration Defense Audit Banking Travel and holiday Forex Trading Jobs Cheap Car Insurance Opening the Book Safe Chemical Act Presspeople System Software Plan Life Insurance Top Best Home Improvements Cheap Car Insurance Auto Parts and Service Swiss Business Acting in Real Time Fitness Equipment Tips Bodybuilding Tips Search Engine Optimization Cardio Tips Beauty Salon Express The Best Advice Lawyer Advice Associated With Online Payday Spa and Wellness Center Packages Holiday Travel European Countries Tours Small Business Finance Electronic Cigarette Commercial Law Advice on Travel Planning Home and Family All System Education Graphic Visual Photo business between countries Shop Online Financial Security Authority Latest Fashion Trends Photoshop Wallpaper Real Estate Agents Micro Cogeneration Beauty Products Business Travel Insurance International Trucks For Sale Hair Tonic Top Web Design Business Financial Touring Start Vehicle Emissions Inspection Business Service Delivery Insurance and Finance Web Design Business Shopping Online Insurance Processing Systems Electric System Vehicle Blood Medicine European Vehicle Market Pharmaceutical Section Home sale Beauty Therapy Acupuncture Recipes Kitchen Restaurant Hardwood Flooring Resident Services The Masterchef Employment and the Economy Free Web Design Paint Creations Travel Insurance SEO Consulting Services Car Insurance Loans Doctors Dental Care Vehicle Wash Systems Search Engine Marketing Online Education Schools Natural Beauty Site Cheap Wedding Dresses annuaire automobile episiotomy and pregnant Westerly Lawyers Healthcare Travel Vacations Cheap iPhone Specifications The ReaL Estate Event Online Pharmacy and Drugstore Music Video Art CareCredit Cloud Trading Strategy House Cleaning Services Interoperability the talent agency Good Home Design shooting simulator Independent Port Services The Hotel Sax The Digital Money Booking Tickets and Hotels Online Business Loans Department of Pharmacy Law Free Credit Report football development Trending in Entertainment Prison Education Sexy Lingerie Wood Flooring Ideas Dealer Optics and Ophthalmology Car Insurance Online Urbanism and Architecture Electronic money International Conference on Education Dental Care Auto Repair Shop Auto Repair Advice Guide Dental Clinic Online Pharmacy Debt Consolidation Loans Free Software Smartphone Advice on benefits Insurance Providence Real Estate Product Research Analyst Product Research Facilitator Fashion Magazine Substance Abuse Education And Technology Marketing Strategy The Best Payday Advance Incident Report Criminal Accounting Books Caring for Pets Real Estate Financing Banking Software Solutions Financial Solutions Credit Loans Full Service Research Agency Discover our free games Business Prospects Trade Online Restaurant Hood Cleaning how to start a business Women's Health and Beauty Payday Loans Criminal Attorney Lawyers Travel and Tourism Fashion Designer The Food Products Fitness and Sports The Beginner's Guide to Businesses Tips To Make SEO Techniques Online Payday Loans Medical Advocate Englisch Training Online Drivers Education Auto Parts and Service Best hotels cheap sport shoes Dental Work Insurance Company Android Phones Financial Advice Service Mobile phone Free Credit Report  The Hair Tonic Advantage Car Rental Information Civil Law Information Payday Cash Loans Payday Cash Loans Advance Affordable Auto Insurance Effective Quality Services Car seats Product Interactions Specialist Medicina Natural Traveller and Hotel European Investment Bank Vehicle Electrical System Pet Food Shop Online Lawyer Employment Plaza Ballroom Weddings Art School The best form of insurance solutions Advice on benefits Insurance Medical coding Tutor Buying Safe Products Free Online Game Famous Fashion Designers Education in Music Virtual Currency Systems Learn Trading Folktronica music Digital currency Manufacturing Engineering Technology Fashionista The Money System Explained Good Marketing In Business Technology Ipad Real Estate Bubble CarePass for Android Business Direct Marketing Carpet Cleaner Natural Beauty Products Seo Web Marketing Business Prospects Trade Online Tool House Cleaner Bathing Equipment Financial Solutions Credit Loans Business Insurance Best Supplements Online Affiliate Marketing Web Design Jobs Online Business Degrees Travel and Leisure Hotel Property Residential and Commercial Real Estate All About Medical Bankruptcy Prevent Child Obesity Handbag and Shoes Education of Children Women Management Free Online Slots Games Healthy Life PET online Interzoo Sunrise Health and Rehabilitation Center Presspeople System Software Baidu Software Center Scientific Entrepreneurship Automotive Advertising Agencies Health and Care Virtual private network Student Education Technosound Information network energy sources Niche Dating Classic Car Restoration Defense Audit Banking Travel and holiday Safe Chemical Act Leader in internet information Music Electric The Marketing verb translation country island FILM LITERATURE GOLD STATUS A Short History of Movies Sexy Lingerie Classified ads Inspire Home Design Trauma Clinic Finance Investment Business Marketing Acting in Real Time Glasgow Tourism Herbal Medicine Cheap Car Insurance Quotes Health Pregnancy Professional Graphic and New Media Designers Legal Connect Network Generating Money Online Oregon health plan Slow Cooker Recipes Best Internet Business Terms and Conditions of Sale Products for Treating Acne Scars Hardwoods Furniture Green Tea Fitness Equipment Tips Bodybuilding Tips Forex Trading Article Marketing Colon Cleanse Tips Hair Loss Tips List Building Search Engine Optimization Cardio Tips Aromatherapy Tips Medical Weight Loss Clinic The Benefits Of Moving Insurance Travel Advice Online Dating Security Network Information Green Energy Scheme Group Auto International Business Telecommunication International All Medicine Reviews Marketplace Real Estate Review Clothing Style Management Consulting Real estate Natural Medicine Treatment Natural Beauty Skin Care Products Shop online Marketing Bank rent car guide Fishing Games cheap website traffic Health and Beauty Gambling football Clothes and Accessories Garden and Landscaping Portal Game Online E-commerce Business Car Accident Lawyer Criminal Law Best free Android apps Hotel and Travel Jobs Technology Film Industry Free Music Downloads Solar Installation Search Engine Optimization Life Technologies Football Betting Site Substance Abuse Apartments home improvement contractor job Luxury Car News Law Products and Services Business Web Hosting Company Complaints Diabetes Drug Abuse Marketing Product Make Money Online Living Without Money Apartments Luxury Car News Law Products and Services Growth Technologies Articles on business growth technologies information Health Insurance Management Advisors System Solar Panel Online Trading The Best of Insurance Payday Loans for Bad Credit Financial Solutions Credit Loans Ensure Insurance Plan Financial Management Team Payday Loans Reviews Distributed File System Student Loan Payments Cheap Insurance in Los Angeles Favorite Fashion Styles The Best Savings Rates Manage Student Loans Webshop europe business guide Shop Personal Loans debt consolidation loans Personal Loan Repayment Chiropractic Tables Webdesign Management Concepts Android Software Free Internet Solution the online casino Best Small Business Blogs Sound Beginnings Automotive Electrical Systems Skin Care in Centrum Master Ethique Cher Client Agency Law Sell Products Online Mens Shoes Strategy Business Development Women's shoes Headache Causes Shop Online Clothing Online Pharmacy Healthy Aging Battle Games best electric vehicle Commercial Real Estate Cosmetic Beauty Product Health Medicine Pharmacy Image of the Orient Fashion Jewellery

Blog Archive