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Impact of obesity on haematopoietic stem cells

Research is showing that age and environmental stresses can lessen the healthy diversity of cells in our blood-making machinery

Researchers have highlighted the pernicious effect of obesity on the long-term health of haematopoietic stem cells (blood-making stem cells). The study, led by researchers at the Cincinnati Children's Cancer and Blood Diseases Institute, was conducted largely in genetic models of obese mice and showed that obesity causes durable and harmful changes to the haematopoietic stem cell compartment.

"There is now an understanding that the blood stem cell compartment is made up of numerous cell subsets," said Dr Damien Reynaud, 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 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.

The paper, ‘Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression’, was published in the Journal of Experimental Medicine.

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.

These microscopic images show bone marrow cellularity and composition in a non-obese control mouse (top) and in a genetically modified obese mouse (bottom). In the bottom microscopic image, bone marrow cells from a genetically modified obese mouse exhibit diminished cellularity and altered composition (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.

Investigators stated that 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 leukaemia and other blood diseases. The study raises questions about the use of haematopoietic 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," added Reynaud. "We want to better understand the molecular alterations in obesity to predict potential risks associated with the therapeutic use of stem cells isolated from obese donors." 

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