Featured Research

from universities, journals, and other organizations

Protein essential for cell division in blood-forming stem cells discovered

Date:
December 5, 2010
Source:
University of Michigan
Summary:
Researchers have discovered that a protein known to regulate cellular metabolism is also necessary for normal cell division in blood-forming stem cells. Loss of the protein results in an abnormal number of chromosomes and a high rate of cell death.

A colony of blood-forming stem cells after seven days in culture.
Credit: Image courtesy of Daisuke Nakada

University of Michigan researchers have discovered that a protein known to regulate cellular metabolism is also necessary for normal cell division in blood-forming stem cells. Loss of the protein results in an abnormal number of chromosomes and a high rate of cell death.

Related Articles


The finding demonstrates that stem cells are metabolically different from other blood-forming cells, which can divide without the protein, Lkb1. This metabolic difference could someday be used to better control the behavior of blood-forming stem cells used in disease treatments, said Sean Morrison, director of the U-M Center for Stem Cell Biology, which is based at the Life Sciences Institute.

"This raises the possibility that, in the future, we may be able to modulate stem cell function --when treating degenerative diseases or when performing cell therapies -- by altering the metabolism of the cells," said Morrison, a Howard Hughes Medical Institute investigator. "It opens up a whole new area of inquiry that, until now, had not been recognized."

Lkb1 is a protein kinase that acts as a tumor suppressor and coordinates cellular metabolism with cell growth. Specifically, Lkb1 (and another kinase called AMPK) helps maintain a balance between a cell's internal energy production and the process of cell division, sending signals to halt division when a cell lacks the energy needed to execute the process.

Few studies have examined stem cell metabolism. There's been a widespread assumption among biologists that basic metabolic processes are broadly similar in most cell types.

In many types of cells, deleting the genes that make Lkb1 and AMPK leads to tissue overgrowth and the formation of tumors, presumably because the cells no long receive signals telling them to stop dividing.

Morrison's team deleted the two genes in blood-forming stem cells of mice -- the first time these genes have been "knocked out" in stem cells -- then observed and measured the effects. Their results are reported in the Dec. 2 edition of the journal Nature.

"One obvious prediction you'd make, based on the outcome of previous studies, is that the cells would start to hyper-proliferate," said Daisuke Nakada, a research fellow at the U-M Life Sciences Institute and first author of the Nature paper.

"But that's not what we saw at all," Morrison said. "Deletion of the Lkb1 gene induced cell death in blood-forming stem cells, and the cells disappeared faster than anything we've ever seen before."

The observed cell death is likely due to defects in energy production within the stem cells, as well as another effect observed by Morrison's team. They found that knocking out the Lkb1 gene derailed the cell division process, leading to unhealthy daughter cells with the wrong number of chromosomes.

Normal cell division, known as mitosis, results in the separation of replicated chromosomes and the formation of two daughter nuclei with identical sets of chromosomes and genes. Inside the dividing cell's nucleus, a structure called a mitotic spindle pulls chromosomes into the daughter cells in an orderly fashion.

Morrison's team found that deleting Lkb1 resulted in mitotic chaos. Multiple mitotic spindles formed, pulling the chromosomes into a tangled mess.

"The cells that survive this mayhem have an abnormal number of chromosomes, which we think leads to the death of a lot of cells," Morrison said. "So Lkb1 is acutely required for blood-forming stem cells to divide properly."

In addition to Nakada and Morrison, the other author of the Nature paper is Thomas Saunders, a research assistant professor in the Department of Internal Medicine at the Medical School and managing director of U-M's Transgenic Animal Model Core.

The work was supported by the Howard Hughes Medical Institute. Flow cytometry was partially supported by a National Institutes of Health grant to the U-M Comprehensive Cancer Center. Nakada was supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science.

Two other papers examining Lkb1's role in regulating cellular metabolism in blood-forming stem cells appear in the same edition of Nature. Both papers are by Harvard University researchers and report results consistent with the U-M findings.


Story Source:

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


Journal Reference:

  1. Ellen M. Durand, Leonard I. Zon. Stem cells: The blood balance. Nature, 2010; 468 (7324): 644 DOI: 10.1038/468644a

Cite This Page:

University of Michigan. "Protein essential for cell division in blood-forming stem cells discovered." ScienceDaily. ScienceDaily, 5 December 2010. <www.sciencedaily.com/releases/2010/12/101201134200.htm>.
University of Michigan. (2010, December 5). Protein essential for cell division in blood-forming stem cells discovered. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2010/12/101201134200.htm
University of Michigan. "Protein essential for cell division in blood-forming stem cells discovered." ScienceDaily. www.sciencedaily.com/releases/2010/12/101201134200.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Dinosaur Species Found in Museum Collection

New Dinosaur Species Found in Museum Collection

Reuters - Innovations Video Online (Nov. 27, 2014) A British palaeontologist has discovered a new species of dinosaur while studying fossils in a Canadian museum. Pentaceratops aquilonius was related to Triceratops and lived at the end of the Cretaceous Period, around 75 million years ago. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. 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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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