Navigation Links
New insights into cellular reprogramming revealed by genomic analysis
Date:5/28/2008

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 Universitys 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.

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:

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

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

  3. 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.

  4. 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.


'/>"/>

Contact: Nicole Davis
ndavis@broad.mit.edu
617-258-0952
Broad Institute of MIT and Harvard
Source:Eurekalert

Related biology technology :

1. Pharmaceuticals & Biotechs to Share Insights for Developing Leaders in a Fast-Paced, Competitive Industry
2. PAREXEL Experts to Offer Insights Into Outsourcing Best Practices at 17th Annual Partnerships with CROs Conference
3. PAREXEL to Present Leading Insights Regarding Key Industry Topics at 20th Annual Drug Information Association EuroMeeting
4. New insights into the fate of anti-parasitics in manure and manured soils
5. Arena Pharmaceuticals Selected to Join New NASDAQ NeuroInsights Neurotech Index
6. Medivation Selected as Founding Member of New NASDAQ(R) NeuroInsights(R) Neurotech Index
7. Dental Implant Market Insights Webinar
8. Sangamo BioSciences Announces Presentation of Phase 1 Data of ZFP Therapeutic at International Society for Cellular Therapy (ISCT) Meeting
9. Having Penetrated Israels Domestic Telephony Market, 012 Smile.Communications Prepares for Its Next Goal: Entering Israels Cellular Market
10. Cellular construction methods emulated
11. First Live U.S. Demonstration of Cellvizio GI In Vivo Cellular Imaging Technology to Occur at Johns Hopkins Conference
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/6/2016)... ... February 06, 2016 , ... Contact:, ... Center for Excellence in Education Sponsors Teacher Training Program , Bite of Science ... – The Center for Excellence in Education (CEE) will sponsor a Bite of ...
(Date:2/5/2016)... 2016 Australian-US drug discovery and development company, Novogen ... of a new Chairman, Mr John O,Connor , and ... James Garner , has also been formally ... Acting CEO, Mr Iain Ross , will resume his ... James Garner , has also been formally appointed to ...
(Date:2/4/2016)... , ... February 04, 2016 ... ... presented by Bloomsburg University’s Digital Forensics Club, takes place February 5-6 at ... event features 20+ speakers and activities such as workshops and competitions for ...
(Date:2/4/2016)... EDISON, N.J. , Feb. 4, 2016 ... company focused on the development and commercialization of targeted ... BIO CEO & Investor Conference 2016, to be held ... and Source Capital Group,s 2016 Disruptive Growth & Healthcare ... on February 10-11, 2016. James Sapirstein ...
Breaking Biology Technology:
(Date:2/1/2016)... , February 1, 2016 Rising ... to drive global touchfree intuitive gesture control market ... Rising sales of consumer electronics coupled with new ... market size through 2020   ... coupled with new technological advancements to drive global touchfree ...
(Date:1/25/2016)...   Unisys Corporation (NYSE: UIS ) today announced ... International Airport, New York City , to help ... to enter the United States using passports ... pilot testing of the system at Dulles last year. The ... during January 2016. --> pilot testing of the ...
(Date:1/20/2016)... , Jan. 20, 2016 A market that ... directly benefit from the explosion in genomics knowledge. Learn ... Sound Research. A range of dynamic trends are pushing ... - personalized medicine - pharmacogenomics - pathogen evolution - ... large markets - greater understanding of the role of ...
Breaking Biology News(10 mins):