Unrecognised role of iron in neutrophil differentiation

In Cre/Lox mouse models, functional disruption of iron regulatory proteins (IRPs) leads to halted differentiation of haematopoietic stem cells (HSCs) into granulocytes at later stages. Transcriptome analysis suggests a role for IRPs in cellular metabolism during neutrophil differentiation.

The findings were presented by Dr Bruno Galy (German Cancer Research Centre, Germany) during the Presidential Symposium [1]. Using a conditional gene knock-out (KO) mouse model to disrupt IRPs, the research team reported that acute loss of IRPs resulted in microcytic anaemia and bone marrow aplasia, which was associated with a corresponding decrease of myeloid cell and erythrocyte counts in peripheral blood. Increased counts of stem and multipotent progenitor cells led to an enlargement of the stem cell compartment. Surprisingly, while common progenitors were amplified in the KO compared with the control mice, increased numbers of differentiated cells were not observed.

The research team concluded that IRPs are important for normal haematopoiesis and differentiation. Notably, neutrophil counts, but not monocyte counts, were substantially decreased in the KO compared with the control mice.

Reciprocal bone marrow transplantation experiments supported a specific role for IRPs in neutrophil differentiation. While wildtype cells could differentiate normally when transplanted into KO mice, KO cells failed to differentiate normally when transplanted into wildtype mice. Transcriptome profiling of neutrophils at different stages of differentiation revealed that the immature neutrophils of KO cells had many differentially expressed genes related to cellular metabolism relative to wildtype neutrophils.

“IRPs seem dispensable for the expansion of haematopoietic stem and progenitor cells,” Dr Galy concluded. “Our main finding is that IRP function is not only important for erythrocyte differentiation but also for neutrophil differentiation.”

1. 
   
   1. Bonadonna M, et al. A novel role for iron regulatory proteins in hematopoiesis. EHA25 Virtual, 11-21 June 2020, Abstract S104.

Posted on 28 August, 202018 March, 2024