Genetic abnormalities identified in pluripotent stem cell lines

Jan 06, 2011

A multinational team of researchers led by stem cell scientists at the University of California, San Diego School of Medicine and Scripps Research Institute has documented specific genetic abnormalities that occur in human embryonic (hESC) and induced pluripotent stem cell (iPSC) lines. Their study, "Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture" will be published in the January 7 issue of the journal Cell Stem Cell.

The published findings highlight the need for frequent genomic monitoring of pluripotent stem cells to assure their stability and clinical safety.

"We found that human (hESCs and iPSCs) had higher frequencies of genomic aberrations than other cell types," said Louise Laurent, MD, PhD, assistant professor in the UCSD Department of Reproductive Medicine and first author on the study. "Most strikingly, we observed a higher frequency of genomic duplications in hESCs and deletions in iPSCs, when compared to non-pluripotent samples."

The ability of human to become every cell type in the body has made them potential sources of differentiated cells for cell replacement therapies. "Since genetic aberrations are often associated with cancers, it is vital that cell lines destined for clinical use are free from cancer-associated genomic alterations," said senior author Jeanne F. Loring, PhD, professor and Director of the Center for Regenerative Medicine at the Scripps Research Institute.

The team identified regions in the genome that had a greater tendency to become abnormal in pluripotent cell lines. With hESCs, the observed abnormalities were most often duplications near pluripotency-associated genes; in iPSC lines, there were duplications involving genes and deletions associated with .

These changes could not have been detected by traditional microscopic techniques such as karyotyping. The team instead used a high-resolution molecular technique called "single nucleotide polymorphism" (SNP) analysis, which allowed them to look for genetic changes at more than a million sites in the human genome.

"We were surprised to see profound genetic changes occurring in some cultures over very short periods of time, such as during the process of reprogramming somatic cells into iPSCs and during differentiation of the cells in culture," Laurent said. "We don't know yet what effects, if any, these genetic abnormalities will have on the outcome of basic research studies or clinical applications, and we need to find out."

Loring concluded: "The results of the study illustrate the need for frequent genomic monitoring of pluripotent stem cell cultures. SNP analysis has not been a part of routine monitoring of hESC and iPSC cultures, but our results suggest that perhaps it should be."

Explore further: Team publishes evidence for natural alternative to antibiotic use in livestock

add to favorites email to friend print save as pdf

Related Stories

New type of human stem cell may be more easy to manipulate

Jun 08, 2010

Researchers from the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute have a developed a new type of human pluripotent stem cell that can be manipulated more readily ...

Reprogrammed mouse fibroblasts can make a whole mouse

Jul 23, 2009

In a paper publishing online July 23 in Cell Stem Cell, a Cell Press journal, Dr. Shaorong Gao and colleagues from the National Institute of Biological Sciences in Beijing, China, report an important advance in the charac ...

Memories of the way they used to be

Sep 18, 2009

A team of researchers from the University of California, San Diego School of Medicine and the Salk Institute for Biological Studies in La Jolla have developed a safe strategy for reprogramming cells to a pluripotent ...

Recommended for you

Researchers capture picture of microRNA in action

Oct 30, 2014

Biologists at The Scripps Research Institute (TSRI) have described the atomic-level workings of "microRNA" molecules, which control the expression of genes in all animals and plants.

Blocking a fork in the road to DNA replication

Oct 30, 2014

A team of Whitehead Institute scientists has discovered the surprising manner in which an enigmatic protein known as SUUR acts to control gene copy number during DNA replication. It's a finding that could shed new light on ...

Cell division, minus the cells

Oct 30, 2014

(Phys.org) —The process of cell division is central to life. The last stage, when two daughter cells split from each other, has fascinated scientists since the dawn of cell biology in the Victorian era. ...

A new method simplifies the analysis of RNA structure

Oct 30, 2014

To understand the function of an RNA molecule, similar to the better-known DNA and vital for cell metabolism, we need to know its three-dimensional structure. Unfortunately, establishing the shape of an RNA ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Quantum_Conundrum
1 / 5 (1) Jan 06, 2011
Translation:

"Stem cells are about as likely to give you a new type of cancer as they are to cure anything."

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.