An iron rheostat controls hematopoietic stem cell fate

Yun Ruei Kao, Jiahao Chen, Rajni Kumari, Anita Ng, Aliona Zintiridou, Madhuri Tatiparthy, Yuhong Ma, Maria M. Aivalioti, Deeposree Moulik, Sriram Sundaravel, Daqian Sun, Julie A. Reisz, Juliane Grimm, Nuria Martinez-Lopez, Stephanie Stransky, Simone Sidoli, Ulrich Steidl, Rajat Singh, Angelo D'Alessandro, Britta Will

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)378-397.e12
JournalCell Stem Cell
Issue number3
StatePublished - Mar 7 2024


  • Tip60/KAT5
  • aging
  • gene regulation
  • hematopoiesis
  • iron
  • metabolism
  • stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


Dive into the research topics of 'An iron rheostat controls hematopoietic stem cell fate'. Together they form a unique fingerprint.

Cite this