Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New insights into cellular reprogramming revealed by genomic analysis

30.05.2008
Research collaboration of Harvard, Whitehead Institute, and Broad Institute uncovers critical molecular events underlying reprogramming of differentiated cells to a stem cell state

The ability to drive somatic, or fully differentiated, human cells back to a pluripotent or “stem cell” state would overcome many of the significant scientific and social challenges to the use of embryo-derived stem cells and help realize the promise of regenerative medicine.

Recent research with mouse and human cells has demonstrated that such a transformation (“reprogramming”) is possible, although the current process is inefficient and, when it does work, poorly understood. But now, thanks to the application of powerful new integrative genomic tools, a cross-disciplinary research team from Harvard University, Whitehead Institute, and the Broad Institute of MIT and Harvard has uncovered significant new information about the molecular changes that underlie the direct reprogramming process. Their findings are published online in the journal Nature.

“We used a genomic approach to identify key obstacles to the reprogramming process and to understand why most cells fail to reprogram,” said Alexander Meissner, assistant professor at Harvard University’s Department of Stem Cell and Regenerative Biology and associate member of the Broad Institute, who led the multi-institutional effort. “Currently, reprogramming requires infecting somatic cells with engineered viruses. This approach may be unsuitable for generating stem cells that can be used in regenerative medicine. Our work provides critical insights that might ultimately lead to a more refined approach.”

... more about:
»Reprogramming »Stem »genomic »partially »reprogrammed

Previous work had demonstrated that four transcription factors — proteins that mediate whether their target genes are turned on or off — could drive fully differentiated cells, such as skin or blood cells, into a stem cell-like state, known as induced pluripotent stem (iPS) cells. Building off of this knowledge, the researchers examined both successfully and unsuccessfully reprogrammed cells to better understand the complex process.

“Interestingly, the response of most cells appears to be activation of normal ‘fail safe’ mechanisms”, said Tarjei Mikkelsen, a graduate student at the Broad Institute and first author of the Nature paper. ”Improving the low efficiency of the reprogramming process will require circumventing these mechanisms without disabling them permanently.”

The researchers used next-generation sequencing technologies to generate genome-wide maps of epigenetic modifications — which control how DNA is packaged and accessed within cells — and integrated this approach with gene expression profiling to monitor how cells change during the reprogramming process. Their key findings include:

Fully reprogrammed cells, or iPS cells, demonstrate gene expression and epigenetic modifications that are strikingly similar, although not necessarily identical, to embryonic stem cells.

Cells that escape their initial fail-safe mechanisms can still become ‘stuck’ in partially reprogrammed states.

By identifying characteristic differences in the epigenetic maps and expression profiles of these partially reprogrammed cells, the researchers designed treatments using chemicals or RNA interference (RNAi) that were sufficient to drive them to a fully reprogrammed state.

One of these treatments, involving the chemotherapeutic 5-azacytidine, could improve the overall efficiency of the reprogramming process by several hundred percent.

“A key advance facilitating this work was the isolation of partially reprogrammed cells,” said co-author Jacob Hanna, a postdoctoral fellow at the Whitehead Institute, who recently led two other independent reprogramming studies. “We expect that further characterization of partially programmed cells, along with the discovery and use of other small molecules, will make cellular reprogramming even more efficient and eventually safe for use in regenerative medicine.”

Nicole Davis | EurekAlert!
Further information:
http://www.broad.mit.edu
http://www.harvard.edu
http://www.wi.mit.edu

Further reports about: Reprogramming Stem genomic partially reprogrammed

More articles from Life Sciences:

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Will Earth still exist 5 billion years from now?

08.12.2016 | Physics and Astronomy

Oxygen can wake up dormant bacteria for antibiotic attacks

08.12.2016 | Health and Medicine

Newly discovered bacteria-binding protein in the intestine

08.12.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>