The Microbiota Regulates Hematopoietic Stem Cell Fate Decisions by Controlling Iron Availability in Bone Marrow

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Jan 23

PMID 35065706

Authors

Dachuan Zhang

Xin Gao

Huihui Li

Daniel K Borger

Qiaozhi Wei

Eva Yang

Chunliang Xu

Sandra Pinho

Paul S Frenette

Affiliations

Soon will be listed here.

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.

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