Featured Research

from universities, journals, and other organizations

Long-held assumption of gene expression in embryonic stem cells challenged

Date:
July 3, 2013
Source:
Whitehead Institute for Biomedical Research
Summary:
Researchers have determined that the transcription factor Nanog, which plays a critical role in maintaining the self-renewal of embryonic stem cells, is expressed in a manner similar to other pluripotency markers. This finding contradicts the field’s presumptions about this important gene and its role in the differentiation of embryonic stem cells.

When the reporter for Nanog is inserted upstream of the gene, the reporter does not faithfully represent the gene's activity (lower left, green), compared with a reporter inserted downstream of the gene (lower right, red). To track cell locations, nuclei were marked blue (upper right).
Credit: Image courtesy of Whitehead Institute for Biomedical Research

Whitehead Institute researchers have determined that the transcription factor Nanog, which plays a critical role in the self-renewal of embryonic stem cells, is expressed in a manner similar to other pluripotency markers. This finding contradicts the field's presumptions about this important gene and its role in the differentiation of embryonic stem cells.

A large body of research has reported that Nanog is allelically regulated -- that is, only one copy of the gene is expressed at any given time -- and fluctuations in its expression are responsible for the differences seen in individual embryonic stem (ES) cells' predilection to differentiate into more specialized cells. These studies relied on cells that had a genetic marker or reporter inserted in the DNA upstream of the Nanog gene. This latest research, published in this week's edition of the journal Cell Stem Cell, suggests that results from studies based on this approach could be called into question.

To quantify the variations in Nanog expression, Dina Faddah, a graduate student in the lab of Whitehead Institute Founding Member Rudolf Jaenisch, looked at hundreds of individual mouse ES cells with reporters inserted immediately downstream of the Nanog gene. One Nanog allele had a green reporter, while the other had a red reporter, allowing Faddah to determine which of the two alleles was being expressed.

After analyzing the results and comparing them to the expression of a "housekeeping" gene and other pluripotency factors, Faddah concluded that, regardless of the cells' growing environment, most ES cells express both Nanog alleles and the variability of this expression corresponds to that of the other genes.

When Faddah tested the established method of inserting a reporter upstream of Nanog, her results reflected the earlier studies' conclusions. However, when she checked the results with other forms of gene expression analysis, she found that the method was not a faithful indicator of Nanog's expression.

"The way the reporter was inserted into the DNA seems to disrupt the regulation of the alleles, so that when the reporter says Nanog isn't being expressed, it actually is," says Faddah.

For Jaenisch, this is an instructional tale that should be heeded by all geneticists.

"Clearly, the conclusions for this particular gene need to be reconsidered," says Jaenisch, who is also a professor of biology at MIT. "And it raises the question for other genes. For some genes, there might be similar issues. For other genes, they might be more resistant to this type of disturbances caused by a reporter."

This work is supported Vertex Scholars Program, the National Science Foundation (NSF), Jerome and Florence Brill Fellowship, Croucher and Ludwig Research Fellowship, the National Institutes of Health (NIH) (1 F32 GM099153-01A1, HD 045022 and R37CA084198).


Story Source:

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


Journal Reference:

  1. Dina A. Faddah, Haoyi Wang, Albert Wu Cheng, Yarden Katz, Yosef Buganim, Rudolf Jaenisch. Single-cell analysis reveals that expression of Nanog is biallelic and equally variable as that of other pluripotency factors in mouse embryonic stem cells. Cell Stem Cell, 3 July 2013 DOI: 10.1016/j.stem.2013.04.019

Cite This Page:

Whitehead Institute for Biomedical Research. "Long-held assumption of gene expression in embryonic stem cells challenged." ScienceDaily. ScienceDaily, 3 July 2013. <www.sciencedaily.com/releases/2013/07/130703120600.htm>.
Whitehead Institute for Biomedical Research. (2013, July 3). Long-held assumption of gene expression in embryonic stem cells challenged. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2013/07/130703120600.htm
Whitehead Institute for Biomedical Research. "Long-held assumption of gene expression in embryonic stem cells challenged." ScienceDaily. www.sciencedaily.com/releases/2013/07/130703120600.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
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