Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression
Abstract
Obesity is a chronic organismal stress that disrupts multiple systemic and tissue-specific functions. In this study, we describe the impact of obesity on the activity of the hematopoietic stem cell (HSC) compartment. We show that obesity alters the composition of the HSC compartment and its activity in response to hematopoietic stress. The impact of obesity on HSC function is progressively acquired but persists after weight loss or transplantation into a normal environment. Mechanistically, we establish that the oxidative stress induced by obesity dysregulates the expression of the transcription factor Gfi1 and that increased Gfi1 expression is required for the abnormal HSC function induced by obesity. These results demonstrate that obesity produces durable changes in HSC function and phenotype and that elevation of Gfi1 expression in response to the oxidative environment is a key driver of the altered HSC properties observed in obesity. Altogether, these data provide phenotypic and mechanistic insight into durable hematopoietic dysregulations resulting from obesity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 27, 2017
- Source ID
- 10.1084/jem.20170690
Entities
People
- Ashwini Hinge
- Bruce J Aronow
- Bryan Goddard
- Damien Reynaud
- David E Muench
- H. Leighton Grimes
- Jose A Cancelas
- Jung-mi Lee
- Marie-dominique Filippi
- Nathan Salomonis
- Vinothini Govindarajah
Organizations
- Cincinnati Children's Hospital Medical Center
- Concern Foundation
- National Institutes of Health
- United States Department of Defense
- University of Cincinnati