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:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...