An iron rheostat controls hematopoietic stem cell fate.
Cell Stem Cell
; 31(3): 378-397.e12, 2024 03 07.
Article
in En
| MEDLINE
| ID: mdl-38402617
ABSTRACT
Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoiesis
/
Iron
Language:
En
Journal:
Cell Stem Cell
Year:
2024
Document type:
Article