Featured Research

from universities, journals, and other organizations

Scientists turn human skin cells directly into neurons, skipping IPS stage

Date:
May 27, 2011
Source:
Stanford University Medical Center
Summary:
Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins, according to a new study. The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish.

Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins, according to a study by researchers at the Stanford University School of Medicine. The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish.

It may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells -- seemingly on the basis of the proteins used to render them pluripotent.

The new research parallels that of the same Stanford group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly.

"We are now much closer to being able to mimic brain or neurological diseases in the laboratory," said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "We may perhaps even be able to one day use these cells for human therapies."

Wernig is the senior author of the research, which will be published online May 26 in Nature. Postdoctoral scholars Zhiping Pang, PhD, Nan Yang, PhD, and graduate student Thomas Vierbuchen share first authorship of the paper. Wernig's laboratory collaborated with that of neuroscientist Thomas Sudhof, MD, the Avram Goldstein Professor in the School of Medicine, on the work.

After their success in laboratory mice -- the results of which were published last year in Nature -- the researchers applied a similar technique to human cells. They first showed that they could convert human embryonic stem cells to neurons by infecting them with a virus expressing the same combination of proteins: transcription factors called Brn2, Ascl1 and Myt1l. They termed the treatment "BAM" for short. BAM treatment readily turned the embryonic stem cells into functional neurons within six days. It also worked on induced pluripotent stem cells.

So then the scientists moved to their big challenge: Could they do the same with human skin cells? In experiments using skin cells from fetuses and newborns, they found that BAM treatment caused these mature skin cells to look more like neurons, but that the resulting cells were unable to generate the electrical signals that neurons use to communicate with one another.

They wondered if there was a missing ingredient. Adding a fourth transcription factor called NeuroD proved to be the tipping point: The skin cells then transformed to functional neurons in the laboratory culture dish within about four to five weeks -- expressing electrical activity and even integrating into and interacting with mouse neurons grown on a laboratory dish.

Although about 20 percent of mouse skin cells can be transformed directly into neurons, only about 2 to 4 percent of human skin cells make functional neurons under the current culture conditions. And while the mouse cells accomplished their switch within just a few days, the human cells required several weeks and generated less-robust electrical signals than naturally derived neurons.

"Clearly mice and humans are different in significant ways," said Wernig, who said that he and his colleagues are now working to optimize the technique and culture conditions to increase the efficiency and speed of the direct transformation.

The direct conversion of skin cells to neurons contrasts with similar research that first transforms skin cells to a pluripotent, or developmentally flexible, state and then coaxes them to become neurons or other specialized cells. A separate team of Stanford researchers recently used this technique to generate patient-specific neurons from a woman with Parkinson's disease. However, that process is labor-intensive and relies on cell lines that may not fully reflect the cell-to-cell diversity that occurs in a natural population. Wernig emphasized that it is important to continue to explore both research techniques.

"The iPS cell approach is doable and has been shown to work," said Wernig. "We need to keep working on both strategies. It's possible that the best approach may vary depending on the disease or the type of research being done."

Additional Stanford researchers involved in the study include graduate student Austin Ostermeier; undergraduates Daniel Fuentes and Troy Yang; postdoctoral scholars Ami Citri, PhD, and Samuele Marro, PhD; and research manager Vittorio Sebastiano.

The research was supported by the Stanford Institute for Stem Cell Biology and Regenerative Medicine, the Ellison Medical Foundation, the Stinehard-Reed Foundation, the Donald E. and Delia B. Baxter Foundation, the New York Stem Cell Foundation and the National Institutes of Health.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. The original article was written by Krista Conger. Note: Materials may be edited for content and length.


Journal Reference:

  1. Zhiping P. Pang, Nan Yang, Thomas Vierbuchen, Austin Ostermeier, Daniel R. Fuentes, Troy Q. Yang, Ami Citri, Vittorio Sebastiano, Samuele Marro, Thomas C. Südhof, Marius Wernig. Induction of human neuronal cells by defined transcription factors. Nature, 2011; DOI: 10.1038/nature10202

Cite This Page:

Stanford University Medical Center. "Scientists turn human skin cells directly into neurons, skipping IPS stage." ScienceDaily. ScienceDaily, 27 May 2011. <www.sciencedaily.com/releases/2011/05/110526131235.htm>.
Stanford University Medical Center. (2011, May 27). Scientists turn human skin cells directly into neurons, skipping IPS stage. ScienceDaily. Retrieved August 31, 2014 from www.sciencedaily.com/releases/2011/05/110526131235.htm
Stanford University Medical Center. "Scientists turn human skin cells directly into neurons, skipping IPS stage." ScienceDaily. www.sciencedaily.com/releases/2011/05/110526131235.htm (accessed August 31, 2014).

Share This




More Health & Medicine News

Sunday, August 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) — A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) — Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) — California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) — Here are three things you need to know about the deadly Ebola outbreak's progression this week. 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