The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow

Dachuan Zhang, Xin Gao, Huihui Li, Daniel K. Borger, Qiaozhi Wei, Eva Yang, Chunliang Xu, Sandra I. Pinho, Paul S. Frenette

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Host microbiota crosstalk is essential for the production and functional modulation of blood-cell lineages. Whether, and if so how, the microbiota influences hematopoietic stem cells (HSCs) is unclear. Here, we show that the microbiota regulates HSC self-renewal and differentiation under stress conditions by modulating local iron availability in the bone marrow (BM). In microbiota-depleted mice, HSC self-renewal was enhanced during regeneration, while the commitment toward differentiation was dramatically compromised. Mechanistically, microbiota depletion selectively impaired the recycling of red blood cells (RBCs) by BM macrophages, resulting in reduced local iron levels without affecting systemic iron homeostasis. Limiting iron availability in food (in vivo) or in culture (ex vivo), or by CD169+ macrophage depletion, enhanced HSC self-renewal and expansion. These results reveal an intricate interplay between the microbiota, macrophages, and iron, and their essential roles in regulating critical HSC fate decisions under stress.

Original languageEnglish (US)
Pages (from-to)232-247.e7
JournalCell Stem Cell
Volume29
Issue number2
DOIs
StatePublished - Feb 3 2022

Keywords

  • erythrophagocytosis
  • fate decision
  • hematopoietic regeneration
  • hematopoietic stem cell
  • iron
  • macrophage
  • microbiota
  • self-renewal

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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