Featured Research

from universities, journals, and other organizations

Scientists find cell fate switch that decides liver, or pancreas?

Date:
February 13, 2014
Source:
Harvard University
Summary:
Stem cell scientists have a new theory for how stem cells decide whether to become liver or pancreatic cells during development. A cell's fate, the researchers found, is determined by the nearby presence of prostaglandin E2, a messenger molecule best known for its role in inflammation and pain. The discovery could potentially make liver and pancreas cells easier to generate both in the lab and for future cell therapies.

A cell’s fate, the researchers found, is determined by the nearby presence of prostaglandin E2, a messenger molecule best known for its role in inflammation and pain.
Credit: Image courtesy of Harvard University

Harvard stem cell scientists have a new theory for how stem cells decide whether to become liver or pancreatic cells during development. A cell's fate, the researchers found, is determined by the nearby presence of prostaglandin E2, a messenger molecule best known for its role in inflammation and pain. The discovery, published in the journal Developmental Cell, could potentially make liver and pancreas cells easier to generate both in the lab and for future cell therapies.

Wolfram Goessling, MD, PhD, and Trista North, PhD, both principal faculty members of the Harvard Stem Cell Institute (HSCI), identified a gradient of prostaglandin E2 in the region of zebrafish embryos where stem cells differentiate into the internal organs. Experiments conducted by postdoctoral fellow Sahar Nissim, MD, PhD, in the Goessling lab showed how liver-or-pancreas-fated stem cells have specific receptors on their membranes to detect the amount of prostaglandin E2 hormone present and coerce the cell into differentiating into a specific organ type.

"Cells that see more prostaglandin become liver and the cells that see less prostaglandin become pancreas," said Goessling, a Harvard Medical School Assistant Professor of Medicine at Brigham and Women's Hospital and Dana-Farber Cancer Institute. "This is the first time that prostaglandin is being reported as a factor that can lead this fate switch and essentially instruct what kind of identity a cell is going to be."

The researchers next collaborated with the laboratory of HSCI Affiliated Faculty member Richard Maas, MD, PhD, Director of the Genetics Division at Brigham and Women's Hospital, to see whether prostaglandin E2 has a similar function in mammals. Richard Sherwood, PhD, a former graduate student of HSCI Co-director Doug Melton, was successfully able to instruct mouse stem cells to become either liver or pancreas cells by exposing them to different amounts of the hormone. Other experiments showed that prostaglandin E2 could also enhance liver growth and regeneration of liver cells.

Goessling and his research partner North, a Harvard Medical School Assistant Professor of Pathology at Beth Israel Deaconess Hospital, first became intrigued by prostaglandin E2 in 2005, as postdoctoral fellows in the lab of HSCI Executive Committee Chair Leonard Zon, MD. It caught their attention during a chemical screen exposing 2,500 known drugs to zebrafish embryos to find any that could amplify blood stem cell populations. Prostaglandin E2 was the most successful hit -- the first molecule discovered in any system to have such an effect -- and recently successfully completed Phase 1b clinical trials as a therapeutic to improve cord blood transplants.

"Prostaglandin might be a master regulator of cell growth in different organs," Goessling said. "It's used in cord blood, as we have shown, it works in the liver, and who knows what other organs might be affected by it."

With evidence of how prostaglandin E2 works in the liver, the researchers next want to calibrate how it can be used in the laboratory to instruct induced pluripotent stem cells -- mature cells that have been reprogrammed into a stem-like state -- to become liver or pancreas cells. The scientists predict that such a protocol could benefit patients who need liver cells for transplantation or who have had organ injury.


Story Source:

The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sahar Nissim, RichardI. Sherwood, Julia Wucherpfennig, Diane Saunders, JamesM. Harris, Virginie Esain, KelliJ. Carroll, GregoryM. Frechette, AndrewJ. Kim, KatieL. Hwang, ClaireC. Cutting, Susanna Elledge, TristaE. North, Wolfram Goessling. Prostaglandin E2 Regulates Liver versus Pancreas Cell-Fate Decisions and Endodermal Outgrowth. Developmental Cell, 2014; DOI: 10.1016/j.devcel.2014.01.006

Cite This Page:

Harvard University. "Scientists find cell fate switch that decides liver, or pancreas?." ScienceDaily. ScienceDaily, 13 February 2014. <www.sciencedaily.com/releases/2014/02/140213153540.htm>.
Harvard University. (2014, February 13). Scientists find cell fate switch that decides liver, or pancreas?. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2014/02/140213153540.htm
Harvard University. "Scientists find cell fate switch that decides liver, or pancreas?." ScienceDaily. www.sciencedaily.com/releases/2014/02/140213153540.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