Corporate Banner
Satellite Banner
Immunology
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Stem Cell Survival Strategy Is Key to Blood and Immune System Health

Published: Monday, February 18, 2013
Last Updated: Monday, February 18, 2013
Bookmark and Share
Stem cells of the aging bone marrow recycle their own molecules to survive and keep replenishing the blood and immune systems as the body ages.

The recycling process, known as autophagy, or self-eating, involves reusing molecules and the chemical energy obtained from these molecules to withstand the killing effect of metabolic stress that intensifies as the body ages.

The discovery, reported online Feb. 6 in the journal Nature, showed that autophagy allows stem cells to avoid the alternative response to stress, which is programmed cellular suicide, in which cells that aren’t up to snuff kill themselves for the greater good.

While this trick of autophagy may help delay the onset of anemia, immune-system failure and other maladies that occur with age, as a survival strategy it is a bit of a compromise, said the senior author of the study, Emmanuelle Passegué, PhD, of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Autophagy might increase cancer risk, she said, by allowing old stem cells to survive despite having accumulated risky mutations over a lifetime.

“Almost all blood malignancies start in the stem cell niche,” said Passegué. Many of the deadliest and most prevalent blood cancers – for example, acute myelogenous leukemia – appear to arise from damaged stem cells and become increasingly common with age.

Trying to keep old stem cells of the blood and immune system functioning well without raising cancer risks is one of the next big challenges in biomedical research, she said.

“Our next step is to look within the stem cells to see what goes wrong as they begin to perform poorly with age.”

Autophagy is a Metabolic Stress Response

The overall finding of the study was that autophagy is triggered in blood, or hematopoietic, stem cells when a genetic switch called FOXO3A is turned on. The researchers showed that the process is not activated in the more mature, specialized cells of the blood or immune system.

“Our study indicates that autophagy is a mechanism of stress response that specifically protects stem cells,” said Passegué. “It’s a way of cleaning up within the cell that liberates amino acids and nutrients so that the stem cell can use that energy to survive being deprived of growth factors in the bone marrow niche where they reside.”

In their experiments, the researchers showed that metabolic stress in hematopoietic stem cells growing in a dish — in this case caused by lack of cytokines, which are involved in cell signaling, and growth factors, which stimulate growth processes in the cell — triggered FOX03A-driven autophagy. Only when these cells were prevented from activating autophagy did they commit suicide instead.

Similarly, in mice deprived of food for 24 hours, hematopoietic stem cells activated autophagy. Notably, mice that were genetically engineered to lack a key component of the autophagy biochemical machinery could not activate autophagy in response to food deprivation and lost hematopoietic stem cells as a result.

Scientists previously proposed that one factor in aging might be that hematopoietic stem cells become less able to undergo autophagy to save themselves. But when Passegué’s lab group compared hematopoietic stem cells from old and young mice, they found that autophagy was always active in old mice, but not in young — and perhaps less stressed — mice.

“We were very surprised,” Passegué said. “We expected that this mechanism would be falling apart in old stem cells.” In fact, the UCSF researchers show the opposite, that old stem cells absolutely rely on autophagy for survival and die when it is blocked.

The age-associated degradation of the bone marrow milieu probably restricts availability of nutrition and growth factors to old stem cells, according to Passegué. Such metabolic stress may cause stem cells to become damaged and to malfunction, she said.

UCSF study co-authors were postdoctoral fellows Matthew Warr, PhD, Ritu Malhotra, PhD, and Damien Reynaud, PhD; associate professor Jayanta Debnath, MD; technician Mikhail Binnewies; graduate student Johanna Flach, and intern Trit Garg. The National Institutes of Health, the California Institute for Regenerative Medicine and the Leukemia and Lymphoma Society Scholars program funded the research.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

How Early Childhood Vaccination Reduces Leukemia Risk
Chronic infections push ‘pre-leukemia’ cells, common in newborns, into malignancy.
Thursday, May 21, 2015
Human Cancer Prognosis Is Related to Newly Identified Immune Cell
A rare population of tumor-associated “good” cells slows cancer.
Monday, October 20, 2014
Type 1 Diabetes Drug Proves Effective in Clinical Trial
Drug developed by UCSF researcher shows promise for blocking advance of disease in earliest stages.
Thursday, August 08, 2013
HIV Testing Increased and Infection Reduced in Africa with Community Intervention
Free mobile HIV testing and counseling, same-day results and post-test support reduces HIV infections by 14 percent.
Thursday, March 07, 2013
Multiple Sclerosis ‘Immune Exchange’ Between Brain and Blood is Uncovered
UCSF finding of movement by disease-causing B cells gives hope for new treatments and diagnostics.
Thursday, November 22, 2012
NIH Awards $15 Million Grant to UCSF-CFAR
UCSF-CFAR awarded more than $15 million over the next five years to continue UCSF-Gladstone AIDS research.
Thursday, October 18, 2012
Research Offers New Hope for HIV/AIDS Patients with Cancer
Proposed treatment for herpes virus that causes Kaposi's sarcoma receives translational research funding.
Thursday, August 23, 2012
New Standards to Improve Diagnosis of Sjögren’s Syndrome
UCSF-led team of international researchers develop criteria to identify autoimmune disease.
Tuesday, August 14, 2012
Researchers Identify a Potential New HIV Vaccine/Therapy Target
Investigators first determine levels of Th17 cells in the gut of sixteen rhesus macaques and then infected them with SIV.
Monday, June 04, 2012
Scientific News
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Experimental MERS Vaccine Shows Promise in Animal Studies
A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Researchers Develop Vaccine that Protects Primates Against Ebola
A collaborative team from The University of Texas Medical Branch at Galveston and the National Institutes of Health have developed an inhalable vaccine that protects primates against Ebola.
Universal Flu Vaccine in the Works
A new study has demonstrated a potential strategy for developing a flu vaccine with potent, broad protection.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Immune System 'On Switch' Breakthrough Could Lead to Targeted Drugs
A crucial 'on switch' that boosts the body's defenses against infections has been successfully identified in new scientific research.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!