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•CPX is a regulator of HSCs and preserves the stem cell state in culture.•CPX-induced HSC maintenance is mediated by intracellular iron chelation, which restricts respiratory capacity and proliferation.

No relevant conflicts of interest to declare.

The majority of adult hematopoietic stem cells (HSCs) are maintained in a dormant state under homeostatic conditions. In contrast, under stressed conditions such as myeloablation and infection, HSCs are known to proliferate and rapidly give rise to downstream progeny. However, it is unclear whether and how HSCs respond to severe anemic conditions. Here we report that HSCs rapidly expand with a biased differentiation towards erythroid cells upon the induction of acute anemia.

No relevant conflicts of interest to declare.

Diamond-Blackfan anemia (DBA) is a bone marrow failure syndrome associated with ribosomal protein (RP) deficiency caused by mutations in RP genes. 25% of patients carry mutations in the RPS19gene. A salient feature of DBA is proliferative arrest of erythroid progenitors. It is still not clear how defects in RPs, which are essential to all cell types, affect the erythroid compartment more severely than the others. Today, DBA patients are treated with glucocorticoids and/or blood transfusions, often for long periods, causing severe adverse effects. We hypothesize that novel drugs with more disease-specific therapeutic mechanisms can be developed and that such drugs will be superior to current therapies. Towards this aim we have developed a method for screening chemical libraries to identify novel drug candidates.