Featured Research

from universities, journals, and other organizations

Scientists create human embryonic stem cells with enhanced pluripotency

Date:
May 6, 2010
Source:
Whitehead Institute for Biomedical Research
Summary:
For the first time, researchers have converted established human induced pluripotent stem cells and human embryonic stem (ES) cells to state that corresponds to that of mouse embryonic stem cells. Mouse embryonic stem cell are more immature and are endowed with greater pluripotency than traditional human ES cells and, importantly, are much easier to propagate and to manipulate.

Whitehead Institute researchers have converted established human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells to a base state of greater pluripotency.

"This is a previously unknown pluripotent state in human cells," says Jacob Hanna, a postdoctoral researcher in the lab of Whitehead Member Rudolf Jaenisch. "It's the first time these cell types have approached the flexibility found in mouse ES cells."

ES cells and iPS cells have attracted much attention because of their potential to mature into virtually any cell type in the body. Because ethical and legal issues have hampered human ES cell research, mouse cells have provided a more viable platform for ES cell studies. However, mouse and human ES cells differ in a number of significant ways, raising the very real possibility that breakthroughs in mouse stem cell science simply won't be reproducible with human stem cells.

Researchers have had a relatively easy time genetically manipulating and preventing differentiation (maturation beyond the base pluripotent state) in mouse ES and iPS cells. But human ES and iPS cells have different sets of expressed genes and depend on different signaling pathways for growth and differentiation than mouse ES and iPS cells, which makes the human cells more difficult to work with.

Because of these biological differences, researchers refer to mouse ES and iPS cells as "nave" while human ES and iPS cells, which teeter on the verge of maturation, are more mature and are referred to as being "primed" for differentiation.

Hanna thought this "primed" state of human cells might be attributable to the way the human ES cell lines are created and stored. To generate ES cell lines, researchers remove cells from an early-stage embryo, called a blastocyst. Once removed from this ball of 80-100 cells, the ES cells are put into serum with other cells to keep the ES cells alive and prevent them from differentiating.

In creating iPS cells, researchers take cells from an adult and insert three to four genes into the cells' genome. These genes reprogram the adult cells to an embryonic stem-cell-like state. Like ES cells, iPS cells are maintained in serum with other cells. Although human and mouse ES and iPS cells are created and handled in identical fashion, human cells inevitably default to the primed state, suggesting that perhaps some step in the process allows the human ES cells to move ever so slightly toward differentiation.

To determine whether ES and iPS cells could be made with traits similar to the analogous mouse cells, Hanna inserted two of the genes used to create iPS cells into established human ES and iPS cell lines. He also added growth factors into the cells' serum. After about three weeks, the human cells became like their mouse counterparts, both morphologically and biochemically.

"That was really exciting," says Jaenisch, who is also a professor of biology at MIT. "But the process required those inserted genes to be expressed, and that is not what he wanted. He wanted to do this without gene insertion."

Because the random insertion of genes can cause neighboring genes to be over- or under-expressed, potentially resulting in cancer or cell death, Hanna screened through hundreds of small molecules for candidates might mimic the function of the inserted genes. Finally, he found a cocktail of four molecules that converts established human ES and iPS cells to the nave state characteristic of mouse ES cells.

Despite this discovery, we still know very little about human ES cells in this nave state.

"I think this really opens things up, and gives us the possibility to define the biological properties of these new cells," says Jaenisch. "For example, we can to study whether gene targeting, which is highly efficient in mouse ES cells but exceedingly inefficient in traditional human ES cells, is improved in the new "nave" human ES cells."

Not only is this line of research important for stem cell scientists, but it may also impact how human ES and iPS cells could be used therapeutically.

"Because the all of the differences between human ES cells and mouse ES cells, it's really important we understand what could be the basis of these differences before we really start proceeding into therapeutic application," says Hanna. "We want to really understand the biology of these cells and need to revisit a lot of the biology and differentiation potential of human ES and iPS cells."

The research is published in the Proceedings of the National Academy of Sciences. The work was supported by Hillel and Liliana Bachrach, Susan Whitehead, the Helen Hay Whitney Foundation, the Genzyme Fellowship, Society in Science, and the Croucher Foundation Limited.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jacob Hanna, Albert W. Cheng, Krishanu Saha, Jongpil Kim, Frank Soldner, John P. Cassady, Christopher J. Lengner, Bryce W. Carey, and Rudolf Jaenisch. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proceedings of the National Academy of Sciences, 2010;

Cite This Page:

Whitehead Institute for Biomedical Research. "Scientists create human embryonic stem cells with enhanced pluripotency." ScienceDaily. ScienceDaily, 6 May 2010. <www.sciencedaily.com/releases/2010/05/100503161235.htm>.
Whitehead Institute for Biomedical Research. (2010, May 6). Scientists create human embryonic stem cells with enhanced pluripotency. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2010/05/100503161235.htm
Whitehead Institute for Biomedical Research. "Scientists create human embryonic stem cells with enhanced pluripotency." ScienceDaily. www.sciencedaily.com/releases/2010/05/100503161235.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
Powered by NewsLook.com
Common Antibiotic Could Lead To Heart-Related Death

Common Antibiotic Could Lead To Heart-Related Death

Newsy (Aug. 20, 2014) Danish researchers discovered patients taking clarithromycin have an increased risk of dying from a heart-related issue. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins