Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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

Join For Free

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 3,300+ scientific posters on ePosters
  • More Than 4,900+ 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

Go-Between Immune Cell is Key to Priming the Body’s Fight Against Cancer
‘Antigen-presenting cell’ activates T cells by alerting them to the presence of tumors.
Friday, July 15, 2016
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Friday, June 24, 2016
Tarantula Toxins Offer Key Insights Into Neuroscience of Pain
Toxins extracted from ornamental baboon tarantula may be used as tools to study disorders ranging from irritable bowel syndrome to epilepsy.
Tuesday, June 07, 2016
Cirrhosis-Causing Cells Converted to Healthy Liver Cells in Mice
New approach that repairs liver from within may be more efficient than cell transplants.
Friday, June 03, 2016
Insight into Bacterial Resilience and Antibiotic Targets
Variant of CRISPR technology paired with computerized imaging reveals essential gene networks in bacteria.
Friday, May 27, 2016
Immune System Implicated in Gastroschisis
UCSF researchers show that the immune system is implicated in gastroschisis. The findings could lead to improved treatments for the belly birth defect.
Tuesday, May 17, 2016
Cytokine Triggers Immune Response at Expense of Blood Renewal
Research highlights promise of Anti-IL-1 drugs to treat chronic inflammatory disease.
Tuesday, April 26, 2016
Tense Tumours Lead to Poorer Prognosis
UCSF researchers have discovered that the chances of survival for patients with pancreatic adenocarcinoma (PDAC) — the most common type of pancreatic cancer — may depend in part on how tense their tumors are.
Tuesday, April 19, 2016
Gene Behind Rare Childhood Syndrome Identified
Online activism by one patient’s mother spurred research collaboration which led to the identification of a new genetic syndrome.
Friday, April 15, 2016
UCSF Immunologist to Head New Parker Institute for Cancer Immunotherapy
Renowned UC San Francisco immunologist Jeffrey Bluestone, PhD, has been named president and CEO of the Parker Institute for Cancer Immunotherapy, a national initiative launched with a $250 million grant from The Parker Foundation.
Thursday, April 14, 2016
How The Bat Got Its Wings
Finding may provide clues to human limb development and malformations.
Wednesday, March 30, 2016
Tricked-Out Immune Cells Could Attack Cancer
New cell-engineering technique may lead to precision immunotherapies.
Wednesday, February 03, 2016
MedImmune, UCSF Launch Collaboration
Top scientists partner to research the progression and biology of RIA diseases.
Thursday, January 14, 2016
Agricultural Intervention Improves HIV Outcomes
A multifaceted farming intervention can reduce food insecurity while improving HIV outcomes in patients in Kenya, according to a randomized, controlled trial led by researchers at UC San Francisco.
Thursday, August 20, 2015
How Early Childhood Vaccination Reduces Leukemia Risk
Chronic infections push ‘pre-leukemia’ cells, common in newborns, into malignancy.
Thursday, May 21, 2015
Scientific News
Breakthrough Flu Vaccine Inhibited by Pre-existing Antibodies
Universal truths – how existing antibodies are sabotaging the most promising new human flu vaccines.
Researchers Develop Software That Could Facilitate Drug Development
AptaTRACE can identify aptamers, potentially speed drug advancement.
Gene Therapy for Metabolic Liver Diseases
Researchers have tested gene therapy in pigs from hereditary tyrosinemia type 1, with corrected liver cells being transplanted into the diseased liver.
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
New Medication Shows Promise Against Liver Fibrosis in Animal Studies
Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure.
Raw Eggs Deemed Safe to Eat
A report published today by the Advisory Committee on the Microbiological Safety of Food (ACMSF) into egg safety has shown a major reduction in the risk from salmonella in UK eggs.
Monitoring TTX Toxin in Shellfish
In a number of small studies, mussels and oysters from the eastern and northern part of the Oosterschelde in Holland were found to contain tetrodotoxin (TTX).
Gene Terapy for Muscle Wasting Developed
New gene therapy could save millions of people suffering from muscle wasting disease.
NIH Begins Yellow Fever Vaccine Trial
NIH has initiated an early-stage clinical trial of a vaccine to protect against yellow fever.
Gene-Editing 'Toolbox' Targets Multiple Genes Simultaneously
Researchers have designed a system that modifies, or edits, multiple genes in a genome at once while minimising unintentional effects.
Scroll Up
Scroll Down
Skyscraper Banner

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!