The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow.
Cell Stem Cell
; 29(2): 232-247.e7, 2022 02 03.
Article
en En
| MEDLINE
| ID: mdl-35065706
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Microbiota
Límite:
Animals
Idioma:
En
Revista:
Cell Stem Cell
Año:
2022
Tipo del documento:
Article
Pais de publicación:
Estados Unidos