Metabolic plasticity and hematopoietic stem cell biology

Abstract

Purpose of review: Hematopoietic stem cells (HSCs) residing in the hypoxic niches can both self-renew and give rise to progeny. Multiple regulatory mechanisms for these cellular processes have been identified. Emerging evidence has revealed that metabolism and bioenergetics play important roles in determining stem cell fate in concert with other regulatory networks. In this review, we will discuss recent advances in this field.

Recent findings: Recent studies have helped define and redefine metabolic regulation of HSCs. Resting quiescent stem cells use primarily anaerobic glycolysis for energy production and this metabolic program is required to maintain a functional quiescent state. However, when they exit this state and rapidly proliferate and differentiate into different blood cell types, a robust up-regulation of energy metabolism is expected to meet the quickly rising energy demand. Dysregulation of metabolism in HSCs results in various blood disorders, including leukemia.

Summary: Energy metabolism and HSC activity influence and interlink each other in a highly sophisticated and orchestrated manner. Understanding metabolic regulation of HSC function has significant implications for HSC-based therapies and leukemogenesis research.

Figure 1. Metabolic plasticity in hematopoietic stem cells

Hematopoietic stem cells (HSCs) residing in the hypoxic niches use primarily glycolysis for energy production. Also, fatty acid metabolism is required for the self-renewal associated asymmetric division in HSCs. Upon differentiation of HSCs, cellular metabolism must be switched to mitochondrial oxidative phosphorylation in order to meet the robust energy demand required for this cellular process. The metabolic reprogramming to mitochondrial aerobic metabolism leads to increased levels of cellular reactive oxygen species that prime HSCs for differentiation.