Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover a switch that controls stem cell pluripotency

16.09.2011
Scientists have found a control switch that regulates stem cell "pluripotency," the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in "adult" cells—those that had become the specialized cells that comprise organs and perform functions.

"It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency," said Prof. Benjamin Blencowe, principal investigator on the study and a Professor in the University of Toronto's Departments of Molecular Genetics and Banting and Best Department of Medical Research. "We're beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications."

The findings were published in the current online edition of the scientific journal Cell.

Alternative splicing works by allowing different segments of genetic messages, also known as messenger RNAs, to be spliced in different combinations as the messages are copied from a gene's DNA. Those combinations make different messenger RNAs, which in turn become different proteins.

In stem cells, scientists have shown that a core set of proteins called transcription factors control pluripotency.

The splicing event discovered by Blencowe's team, including first author on the study Dr. Mathieu Gabut, changes the DNA binding properties of FOXP1 in a way that then controls the expression of the core pluripotency transcription factors, to facilitate maintenance of pluripotency. "As a mechanism that controls those core transcription factors, it's right at the heart of the regulatory process of pluripotency," said Blencowe.

At the same time, the mechanism represses the genes required for differentiation—the process whereby by a stem cell loses "stemness" and becomes a specific cell type that makes up an organ or performs a function.

As well, in collaboration with colleagues including Profs. Jeff Wrana and Andras Nagy in the Samuel Lunenfeld Research Institute at Mount Sinai Hospital, also Professors in U of T's Department of Molecular Genetics, the splicing switch identified by Blencowe's team was shown to play a role in "reprogramming," a potentially therapeutic technique in which researchers coax adult cells back into induced pluripotent stem cells by introducing the core transcription factors. "That's an important area in the field where we need better understanding because reprogramming, especially with human cells, is very inefficient," said Blencowe. "Often when reprogrammed stem cells are not fully reprogrammed they become tumorigenic and can lead to cancer."

Potential applications for stem-cell science include growing cells and tissues to test new drugs or to repair or replace damaged tissues in many diseases and conditions, including heart disease, diabetes, spinal cord injury and Alzheimer's disease.

As well, a better understanding of the mechanisms that regulate pluripotency, cell division and differentiation will provide knowledge of how diseases like cancer arise and suggest more targeted therapeutic approaches.

Blencowe and his lab have recently turned their attention to what might be controlling the factors that control both alternative splicing and the maintenance of stem-cell pluripotency. They have, said Blencowe, a few tantalizing glimpses. "There's still a lot to figure out, but I personally believe there is huge potential in the future. If we can fully understand the regulatory controls that allow us to make uniform populations of fully reprogrammed stem cells, there's no reason why they shouldn't be effective for many different therapies. It will come."

Funding for the study was provided by the C.H. Best Foundation, the Canadian Cancer Society, the Canadian Institutes of Health Research, Genome Canada through the Ontario Genomics Institute, the National Institutes of Health, the Ontario Ministry of Research and Innovation, and the Ontario Research Fund.

Other co-authors on the study: Payman Samavarchi-Tehrani (Centre for Systems Biology, Samuel Lunenfeld Research Institute, and Dept. of Molecular Genetics, U of T); Xinchen Wang, Valentina Slobodeniuc, Dave O'Hanlon, Shaheynoor Talukder, Qun Pan, and Timothy Hughes (Banting and Best Dept. of Medical Research, U of T, and The Donnelly Centre for Cellular and Biomolecular Research, U of T); Hoon-Ki Sung and Knut Woltjen (Centre for Stem Cells and Tissue Engineering, SLRI); Manuel Alvarez (The Donnelly Centre, and the Institute of Biomaterials and Biomedical Engineering, U of T); Esteban Mazzoni, Stephane Nedelec and Hynek Wichterle (Columbia University Medical Center); Peter Zandstra (The Donnelly Centre and IBBE).

Jim Oldfield | EurekAlert!
Further information:
http://www.utoronto.ca

More articles from Life Sciences:

nachricht A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Quantum bugs, meet your new swatter

20.08.2018 | Information Technology

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>