Related Experiment Video
Updated: Mar 7, 2026

Assessment of Cellular Bioenergetics in Mouse Hematopoietic Stem and Primitive Progenitor Cells using the Extracellular Flux Analyzer
Published on: September 24, 2021
Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions
Amelie V Guitart1, Theano I Panagopoulou1, Arnaud Villacreces1
1Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH8 9YL, Scotland, UK.
Abstract:
Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1/Hoxa9-driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation.
More Related Videos
12:20Analysis of Hematopoietic Stem Progenitor Cell Metabolism
Published on: November 9, 2019
07:17Improving the Accuracy of Flow Cytometric Assessment of Mitochondrial Membrane Potential in Hematopoietic Stem and Progenitor Cells Through the Inhibition of Efflux Pumps
Published on: July 30, 2019
Related Concept Videos
Regulation of Hematopoietic Stem Cells
Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
Multipotency of Hematopoietic Stem Cells
Regulation of Angiogenesis and Blood Supply
Hematopoiesis
Fates of Pyruvate
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...