Study explores impact of obesity on bone marrow cells

December 27, 2017, Cincinnati Children's Hospital Medical Center
These microscopic images show bone marrow cellularity and composition in a non-obese control mouse (top) and in a genetically modified obese mouse (bottom). Research data published by the Journal of Experimental Medicine explore the long-term harm obesity causes on the body's hematopoietic (blood-making) stem cell system. The study raises questions about the use of hematopoietic stem cell isolated from obese people in therapeutic transplant procedures. Credit: Cincinnati Children's

New research published in the Journal of Experimental Medicine highlights the pernicious effect of obesity on the long-term health of blood-making stem cells (hematopoietic stem cells).

Published Dec. 27, the study was led by researchers at the Cincinnati Children's Cancer and Blood Diseases Institute. Conducted largely in genetic models of , it shows obesity causes durable and harmful changes to the compartment - the blood-making factory in our bodies.

"There is now an understanding that the blood stem cell compartment is made up of numerous cell subsets," said Damien Reynaud, PhD, the study's principal investigator. "Keeping this compartment healthy is essential to human health. This includes maintaining the diverse pool of blood-making stem cells (hematopoietic stem cells) needed to produce blood cells the body needs to function properly."

Although still poorly understood, research is showing that age and environmental stresses can lessen the healthy diversity of cells in our blood-making machinery. This can include skewing blood cell formation toward myeloid cells and possibly promoting pre-leukemic fates, according to Reynaud and his collaborators.

Reynaud and collaborators, including first author and post-doctoral research fellow Jung-Mi Lee, show that obesity related stresses alter the cellular architecture of the hematopoietic stem cell compartment and reduce its long-term functional fitness. Tests in obese mice show these effects are progressive and that some of the harmful manifestations persist even after researchers normalize the animals' weight through dietary controls.

In this microscopic image, bone marrow cells from a genetically modified obese mouse exhibit diminished cellularity and altered composition. The photo is also part of research published in the Journal of Experimental Hematology that raises questions about the use of hematopoietic stem cells isolated from obese people for therapeutic transplant procedures. Credit: Cincinnati Children's

Mechanistically, Reynaud and colleagues report these alterations of the body's blood-making system appear to be linked to over-expression of a transcription factor called Gfi1 - a regulatory gene that tells other genes what to do. The researchers show that oxidative stresses in the body caused by obesity drive overexpression of Gfi1. When this happens, it produces a lasting alteration of hematopoietic stem cell compartment and molecular mayhem may ensues.

Looking at Lifestyle

Investigators say their study also provides groundwork to investigate how lifestyle choices, such as diet, can durably impact blood formation and may contribute to the development of blood cancer.

Hematopoietic stem cells are an important tool for treating leukemia and other diseases. The study raises questions about the use of hematopoietic stem cells isolated from obese people in therapeutic transplant procedures.

"Little is known about how obesity in marrow donors could affect the quality of the hematopoietic stem cell compartment," Reynaud explains. "We want to better understand the molecular alterations in to predict potential risks associated with the therapeutic use of stem isolated from obese donors."

Explore further: Bacterial infection stresses hematopoietic stem cells

More information: Jung-Mi Lee et al, Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation ofGfi1expression, The Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20170690

Related Stories

Bacterial infection stresses hematopoietic stem cells

August 24, 2017
It has been thought that only immune cells would act as the line of defense during bacterial infection. However, recent research has revealed that hematopoietic stem cells, cells that create all other blood cells throughout ...

Innate reaction of hematopoietic stem cells to severe infections

July 20, 2017
Researchers at the University of Zurich have shown for the first time that hematopoietic stem cells detect infectious agents themselves and begin to divide—that is, without signals from growth factors. This direct production ...

Genetic factors control regenerative properties of blood-forming stem cells

December 5, 2016
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 ...

Inhibiting CDK6 prevents leukemic relapse

January 27, 2015
Despite enormous progress in cancer therapy, many patients still relapse because their treatment addresses the symptoms of the disease rather than the cause, the so-called stem cells. Work in the group of Veronika Sexl at ...

Team identifies emergency response system for blood formation

November 16, 2015
Scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) have determined how the body responds during times of emergency when it needs more blood cells. In a study published in Nature, researchers ...

Acceleration of the G1 phase transit during cell division makes human blood stem cells more powerful

July 10, 2015
For the first time, the research group of Prof. Claudia Waskow at the Carl Gustav Carus Faculty of Medicine at Dresden Technical University is now describing a new mechanism in which the length of the G1 phase of the cell ...

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.