Navigation Links
New method developed by UC San Diego bioengineers gives regenerative medicine a boost
Date:4/23/2009

Bioengineers at UC San Diego have developed a breakthrough method for sequencing-based methylation profiling, which could help fuel personalized regenerative medicine and even lead to more efficient and cost-effective methods for studying certain diseases.

To do this, the researchers, led by Kun Zhang, a bioengineering professor in the UC San Diego Jacobs School of Engineering, developed an accurate assays for quantifying DNA methylation digitally on an arbitrary set of nonrepetitive genomic targets using padlock probes.

Zhang and his group describe the breakthrough in a recent paper published in Nature Biotechnology titled "Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming."

DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence. Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets, and are extremely costly (more than $100,000). The method created by Zhang and his team will allow researchers to perform such assays at a significantly lower cost, he said.

"What we reported in this paper is a novel method that allows us to do target analysis on the subset of the genome where we think the memory could be stored," Zhang said.

"This is a generic method for the analysis of epigenome," he added. "The application to induced pluripotent stem cells is one example to demonstrate the utility of this method. The method we developed would be widely applicable to other area of biomedical sciences, such as the study of cancers or Alzheimer's disease."

Epigenetics is an emerging frontier of science that involves the study of changes in the regulation of gene activity and expression that are not dependent on gene sequence. While epigenetics refers to the study of single genes or sets of genes, epigenomics refers to more global analysis of epigenetic changes across the entire genome.

Zhang's team which includes researchers from Harvard University, Virginia Commonwealth University and the University of Wisconsin, Madison used their novel method to study nuclear reprogramming of differentiated adult human cells into pluripotent stem cells.

"We found that nuclear reprogramming based on the existing retroviral carriers appears to result in over-reprogramming, which will have profound implications on the use of induced pluripotent cells for personalized regenerative medicine," Zhang said. "The surprising finding is that all current similar methods seem to be over re programming so they push the cell fate too far. Once we turn the clock back we want to turn it forward again to a certain tissue type to fixed damage tissues in patients. You want to turn it back just enough. If you turn it back too far it might be hard to bring it back. We found that the first generation of (reprogramming) cocktails that people have developed is not perfect yet. One of the biggest concerns about regenerative medicine is that stem cells can cause tumors. You want to control that."

Zhang and his team are using this new method to compare the use of artificial and natural stem cells.

"Different cells manifest as different types, so there are different layers of information and instructions on top of the genetic code," he said. "This method will help determine whether artificial stem cells can 100 percent mimic natural stem cells. This method helps you determine if, by doing this trick, you can generate a stem cell similar to a natural stem cell. If it is not similar there may be some risk. For example, if you use this method on a mouse and the mouse tends to be shorter and develop a tumor, that's a big concern. This research helps ease those concerns. The big open question is by doing this kind of trick are you able to control the artificial cell 100 percent like a natural stem cell? This is the assay to tell you whether it will do this or not.

"You can use our method to compare all kinds of ideas. It's a relatively generic method that has many different applications," Zhang added.

A key to the team's discovery was the use of programmable DNA chips made with a proprietary Ink-jet printing method by Agilent Technology. Zhang and his group have a patent pending on the method to convert DNA coming out from the programmable chips into padlock probes.

In the meantime, Zhang and his team plan to further their research in this area.

"We have already compared fibroblasts with induced pluripotent stem cells, which was to examine what happened when we turned the clock back," he said. "The natural thing we want to do now is follow the entire path. We want to turn the clock forward and differentiate stem cells into multiple tissue and see how the memory of the cells changes. We want to compare the artificial stem cells with the natural stem cells to see whether the differentiation can work exactly the same efficiency on the artificial stem cells as they do on the natural stem cells.

At least now we have a hint of where we should be looking.

"In addition, a couple of second generation reprogramming method, so called virus-free or transgene-free methods, were reported in Nature and Science recently," Zhang said. "We are in the process of testing whether these new methods can alleviate the artifact we observed."


'/>"/>

Contact: Andrea Siedsma
asiedsma@soe.ucsd.edu
858-822-0899
University of California - San Diego
Source:Eurekalert  

Related biology news :

1. Cold and brown fat raise the prospect of a new method of treating obesity
2. New method for detection of phosphoproteins reveals regulator of melanoma invasion
3. Scientists develop method for comprehensive proteome analysis
4. Engineers develop method to disperse chemically modified graphene in organic solvents
5. Pilot study shows effectiveness of new, low-cost method for monitoring hand hygiene compliance
6. New method for detecting explosives
7. Genomatix gets patent for comparative genomics method
8. Protein function and chromatin structure methods featured in Cold Spring Harbor Protocols
9. New method monitors critical bacteria in wastewater treatment
10. Cold Spring Harbor Protocols features stem cell differentiation, plant RNAi methods
11. Intervention method reduces binge drinking
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New method developed by UC San Diego bioengineers gives regenerative medicine a boost
(Date:1/19/2017)... SANTA CLARA, Calif. , Jan. 19, 2017 ... Valley company enhancing user experience and security for ... provider of next-generation payment processing systems and cybersecurity ... assist more banks, enterprises and financial institutions worldwide ... As part of the end-to-end secure user authentication ...
(Date:1/18/2017)... , Jan. 18, 2017 MedNet ... that supports the entire spectrum of clinical research, ... another record-breaking year for the organization in terms ... in MedNet,s eClinical products and services. The company,s ... marketplace success of iMedNet ...
(Date:1/12/2017)... 2017  Trovagene, Inc. (NASDAQ: TROV ), ... announced that it has signed agreements with seven strategic ... Middle East for commercialization of ... first wave of international distribution agreements for Trovagene,s CLIA ... The initial partners will introduce Trovagene,s liquid ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... DES MOINES, Iowa , Feb. 22, 2017 Origin ... an agricultural biotechnology trait and seed provider, and Arcadia ... -based company that develops and commercializes agricultural productivity traits and ... of a key corn biotechnology product developed in China ... completion of global regulatory trials. ...
(Date:2/22/2017)... Md. and RESEARCH TRIANGLE PARK, N.C., Feb. 22, 2017 ... ) today announced its financial results for the ... "Our annual 2016 financial results reflect continued ... earnings exceeded $700 million," said Martine Rothblatt, Ph.D., ... financial results strengthen our ability to develop and ...
(Date:2/21/2017)... ... February 21, 2017 , ... Genedata, a leading ... today announced the establishment of Genedata Limited as a new subsidiary in the ... expert in life science informatics. Creating the UK subsidiary reinforces Genedata’s commitment to ...
(Date:2/21/2017)... ... ... Creation Technologies, a private company and 25-year leader in ... today announced it has received the ‘Highest Overall Customer Rating’ Service Excellence Award. ... electronics manufacturing services (EMS) providers with annual revenues over $500 million. The award ...
Breaking Biology Technology: