To breathe or not to breathe: The haematopoietic stem/progenitor cells dilemma

C. Piccoli, F. Agriesti, R. Scrima, F. Falzetti, M. Di Ianni, N. Capitanio

Research output: Contribution to journalArticle

Abstract

Adult haematopoietic stem/progenitor cells (HSPCs) constitute the lifespan reserve for the generation of all the cellular lineages in the blood. Although massive progress in identifying the cluster of master genes controlling self-renewal and multipotency has been achieved in the past decade, some aspects of the physiology of HSPCs still need to be clarified. In particular, there is growing interest in the metabolic profile of HSPCs in view of their emerging role as determinants of cell fate. Indeed, stem cells and progenitors have distinct metabolic profiles, and the transition from stem to progenitor cell corresponds to a critical metabolic change, from glycolysis to oxidative phosphorylation. In this review, we summarize evidence, reported in the literature and provided by our group, highlighting the peculiar ability of HSPCs to adapt their mitochondrial oxidative/bioenergetic metabolism to survive in the hypoxic microenvironment of the endoblastic niche and to exploit redox signalling in controlling the balance between quiescence versus active cycling and differentiation. Especial prominence is given to the interplay between hypoxia inducible factor-1, globins and NADPH oxidases in managing the mitochondrial dioxygen-related metabolism and biogenesis in HSPCs under different ambient conditions. A mechanistic model is proposed whereby 'mitochondrial differentiation' is a prerequisite in uncommitted stem cells, paving the way for growth/differentiation factor-dependent processes. Advancing the understanding of stem cell metabolism will, hopefully, help to (i) improve efforts to maintain, expand and manipulate HSPCsâ€..ex vivo and realize their potential therapeutic benefits in regenerative medicine; (ii) reprogramme somatic cells to generate stem cells; and (iii) eliminate, selectively, malignant stem cells.

Original languageEnglish
Pages (from-to)1652-1671
Number of pages20
JournalBritish Journal of Pharmacology
Volume169
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • globins
  • haematopoietic stem/progenitor cells
  • hypoxia inducible factor-1
  • mitochondria
  • NADPH oxidases
  • oxidative phosphorylation
  • redox signalling

ASJC Scopus subject areas

  • Pharmacology

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