Featured Research

from universities, journals, and other organizations

One type of stem cell creates a niche for another type in bone marrow

Date:
August 12, 2010
Source:
Cold Spring Harbor Laboratory
Summary:
Researchers have discovered the precise source of hematopoietic stem cell maintenance and regulation within the bone marrow. In a new study, they report that the HSCs retain their unique features of multipotency and self-renewal in response to signals from another stem cell population, the mesenchymal stem cells, which create a supportive niche for the HSCs.

Hematopoietic stem cells (HSCs) have two unique abilities that are prized by medical researchers: to self-renew and to develop into any kind of blood cell, which enables them to replenish the entire blood and immune system. Scientists have traced these qualities to a distinct locale or niche within the bone marrow that HSCs home in on, but the identity and function of the niche-forming constituents have not been clearly defined.

Related Articles


Now, the precise source of HSC maintenance and regulation within the bone marrow has been discovered by Cold Spring Harbor Laboratory (CSHL) researchers and members of a multi-institutional team. In a study to be published in Nature on August 12th, the collaborators report that the HSCs retain their unique features in response to signals from another stem cell population, the mesenchymal stem cells (MSCs), which create a supportive bone marrow niche for the HSCs.

"This is the first demonstration that one type of stem cell can regulate another type of stem cells," says CSHL scientist Grigori Enikolopov, Ph.D. "Having a detailed understanding of how HSCs are maintained within the niche microenvironment offers new opportunities to better exploit these cells for therapeutic use."

The path to this discovery originates from Enikolopov's efforts to develop reliable ways of distinguishing stem cells from other cell types. Previously, his group found that various types of stem cells express a protein called nestin. In recent years, they have detected and analyzed stem cell populations located in niches throughout the body using mice genetically engineered such that nestin-expressing cells also produce a fluorescent marker, making it possible to visually track these cells.

One location where the CSHL researchers found these nestin-expressing cells was the bone marrow, but these cells proved to not be HSCs. To find the identity and function of these mystery cells, they teamed up with a multi-institutional group led by Paul Frenette, M.D., of Mount Sinai School of Medicine, and which also included scientists from Harvard Medical School and the Albert Einstein College of Medicine.

Examining bone marrow sections from the nestin-expressing mice and based on the presence of various molecules on the populations of cells found within, the team identified the nestin-expressing cells as MSCs. These cells, which outnumber the HSCs 10:1, were either in direct contact with the HSCs or in clusters around them.

"This close proximity suggested that there might be some kind of molecular signaling or cross-talk going on that might control HSC maintenance," explains Enikolopov, who has been investigating the consequence of this kind of cell-cell dialogue during tissue and organ development. "One hypothesis is that this interaction directs and regulates growth by teaching different types of cells where they ought to locate themselves and what they should do there."

This seems to be the case, at least in the bone marrow, as the collaborators found that altering the numbers of MSCs has a corresponding effect on the numbers of HSCs. Increasing the numbers of MSCs by injecting mice with a growth hormone caused HSCs to double in number. Inhibiting MSC proliferation via infusions of growth-inhibiting proteins, on the other hand, was followed by a dip in HSC numbers.

The collaborators also explored the consequence of completely eradicating bone marrow MSCs using genetic tools developed in Enikolopov's lab. The CSHL scientists created mice in which only nestin-expressing cells -- the MSCs -- were programmed to carry a receptor for a toxin molecule. Injecting mice with the toxin thus selectively wiped out the MSCs. As a result, the scientists observed a four-fold reduction in the numbers of HSCs in the bone marrow of these mice. In the absence of bone marrow MSCs, large numbers of HSCs injected into the mice also failed to make their way to the bone marrow.

The collaborators found that genetic factors that are essential for HSC maintenance are highly concentrated within the neighboring MSCs. "The expression of these factors are least 500-fold higher in the MSCs than in other bone marrow cells, which shows why HSCs are so highly dependent on the MSCs," says Enikolopov.

"These results are a definitive indication that the MSCs are required for HSC maintenance as well as their homing to the bone marrow," says Tatyana Michurina, Ph.D., a research investigator in Enikolopov's laboratory who is an expert on both MSCs and HSCs. "After studying them as separate entities for years, it was such a surprise to discover that it was the MSCs that helped the HSCs to remain stem-like and primitive."

"These findings suggest that if we can control the niche, we can also manipulate the HSC population within," says Enikolopov. Pharmacological targeting of the niche might help enhance stem cell production for use in regeneration therapies or might help stave off adverse events like leukemia or other disorders where stem cells proliferate out of control.

The CSHL researchers were supported by a grant from the National Institute of Mental Health and a generous contribution by the Ira Hazan Fund.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Simon Mendez-Ferrer, Tatyana V. Michurina, Francesca Ferraro, Amin R. Mazloom, Ben D. MacArthur, Sergio A. Lira, David T. Scadden, Avi Ma'ayan, Grigori N. Enikolopov & Paul S. Frenette. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 2010; 466 (7308): 829 DOI: 10.1038/nature09262

Cite This Page:

Cold Spring Harbor Laboratory. "One type of stem cell creates a niche for another type in bone marrow." ScienceDaily. ScienceDaily, 12 August 2010. <www.sciencedaily.com/releases/2010/08/100812101020.htm>.
Cold Spring Harbor Laboratory. (2010, August 12). One type of stem cell creates a niche for another type in bone marrow. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2010/08/100812101020.htm
Cold Spring Harbor Laboratory. "One type of stem cell creates a niche for another type in bone marrow." ScienceDaily. www.sciencedaily.com/releases/2010/08/100812101020.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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


Health & Medicine

Mind & Brain

Living & Well

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