Nav: Home

Genetic factors control regenerative properties of blood-forming stem cells

December 05, 2016

FINDINGS

Researchers from the UCLA Department of Medicine, Division of Hematology Oncology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have published two studies that define how key genetic factors affect blood-forming stem cells by either accelerating or hindering the cells' regenerative properties. The findings could one day lead to improved treatments for people undergoing common therapies for cancer such as chemotherapy and radiation.

BACKGROUND

Blood-forming stem cells, or hematopoietic stem cells, are found in the bone marrow. These cells have two unique properties: They can self-renew and, through a process called differentiation, they can form any type of blood cell. A healthy immune system depends on the regenerative abilities of hematopoietic stem cells.

Common cancer therapies such as chemotherapy and radiation can eliminate cancer by killing cancer cells. But these treatments also damage hematopoietic stem cells, which can impede the cells' ability to regenerate blood, slowing the immune system and resulting in a longer, more complicated recovery for people with cancer. Previous research indicated that certain genes may alter hematopoietic stem cells' regenerative capacity by either accelerating or hindering the cells' ability to restore the immune system, but more research was needed to pinpoint the specific genetic activity and effects.

METHOD

One of the new studies focused on a gene called Grb10 that is expressed by hematopoietic stem cells. Grb10's function was previously not known, so to better understand its role, the scientists deleted Grb10 from hematopoietic stem cells in lab dishes and in mice that had received radiation. They found that deleting Grb10 strongly promotes hematopoietic stem cell self-renewal and differentiation.

In the other study, researchers analyzed a protein called DKK1. DKK1 is produced by a gene expressed by a specific "bone progenitor" cell that is present in the "niche," or cellular environment, that surrounds the hematopoietic stem cell. Typically, bone progenitor cells regenerate bone, but scientists had previously hypothesized that these cells also play an important role in regulating hematopoietic stem cells' ability to self-renew and differentiate into other blood cells.

"The cellular niche is like the soil that surrounds the stem cell 'seed' and helps it grow and proliferate," said Dr. John Chute, professor of medicine in the Division of Hematology Oncology in the UCLA David Geffen School of Medicine and the study's senior author. "Our hypothesis was that the bone progenitor cell in the niche may promote hematopoietic stem cell regeneration after injury."

The researchers showed that adding DKK1 to hematopoietic stem cells in lab dishes and mice that had received radiation produced a cascade effect within the cell niche that greatly enhanced hematopoietic stem cells' ability to self-renew and differentiate into other blood cells.

IMPACT

Taken together, the studies uncover two molecular mechanisms that could potentially be manipulated to increase the regenerative properties of hematopoietic stem cells and improve cancer therapy. Scientists can now test drugs that inhibit Grb10 or test the effectiveness of administering DKK1 intravenously to promote immune regeneration in people who have received chemotherapy and radiation or those undergoing bone marrow transplants.
-end-
AUTHORS

Chute, who also is a member of the UCLA Jonsson Comprehensive Cancer Center, is the senior author of both papers. The first author of the Nature Medicine study is Heather Himburg and other authors are Mamle Quarmyne, Xiao Yan, Joshua Sasine, Liman Zhao, Grace Hancock, Jenny Kan, Katie Pohl and Evelyn Tran of UCLA; and Phuong Doan, Nelson Chao and Jeffrey Harris of Duke University.

Other authors of the Cell Reports study are Yan, Himburg, Pohl, Quarmyne, Tran, Yurun Zhang, Tianchang Fang, Kan and Zhao of UCLA; and Doan and Chao of Duke University.

JOURNALS

The studies were published in the journals Nature Medicine (embargo lifts at 11:00 a.m. US Eastern time on Monday, December 5, 2016) and Cell Reports (published on November 1, 2016).



FUNDING


The studies were funded by grants from the National Heart, Lung, and Blood Institute (HL-086998-05), the National Institute of Allergy and Infectious Diseases (AI-067798), a California Institute for Regenerative Medicine Leadership Award (LA1-08014), a National Institute of Allergy and Infectious Diseases' Centers for Medical Countermeasures Against Radiation Pilot Award (2U19AI067773-11), and by the UCLA Broad Stem Cell Research Center.

University of California - Los Angeles Health Sciences

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.