The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Sep 1

PMID 20804973

Citations 592

Authors

Tugba Simsek

Fatih Kocabas

Junke Zheng

Ralph J DeBerardinis

Ahmed I Mahmoud

Eric N Olson

Jay W Schneider

Cheng Cheng Zhang

Hesham A Sadek

Affiliations

Soon will be listed here.

Abstract

Bone marrow transplantation is the primary therapy for numerous hematopoietic disorders. The efficiency of bone marrow transplantation depends on the function of long-term hematopoietic stem cells (LT-HSCs), which is markedly influenced by their hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. Here, we show that LT-HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. We used flow cytometry to identify a unique low mitochondrial activity/glycolysis-dependent subpopulation that houses the majority of hematopoietic progenitors and LT-HSCs. Finally, we demonstrate that Meis1 and Hif-1alpha are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1alpha. These findings reveal an important transcriptional network that regulates HSC metabolism.

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