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Selenoproteins regulate stress erythroid progenitors and spleen microenvironment during stress erythropoiesis

Chang Liao, Ross C. Hardison, Mary J. Kennett, Bradley A. Carlson, Robert F. Paulson and K. Sandeep Prabhu

Key points

  • Selenoproteins, and in particular SelenoW, are required for stress erythroid progenitor proliferation and maturation.

  • Macrophages require selenoproteins to maintain erythropoietic niche competency.

Abstract

Micronutrient selenium (Se) plays a key role in redox regulation through its incorporation into selenoproteins as the 21st amino acid selenocysteine (Sec). Because Se deficiency appears to be a cofactor in the anemia associated with chronic inflammatory diseases, we reasoned that selenoproteins may contribute to erythropoietic recovery from anemia, referred to as stress erythropoiesis. Here, we report that loss of selenoproteins through Se deficiency or by mutation of the Sec tRNA (tRNA [Sec]) gene (Trsp) severely impairs stress erythropoiesis at two stages. Early stress erythroid progenitors failed to expand and properly differentiate into BFU-Es; while late stage erythroid progenitors exhibited a maturation defect that affected the transition of proerythroblasts (ProEs) to basophilic erythroblasts (BasoEs). These defects were, in part, due to the loss of selenoprotein W, whose expression was reduced at both transcript and protein levels in Se-deficient erythroblasts. Mutation of SelenoW in the bone marrow cells significantly decreased the expansion of stress BFU-E colonies, which recapitulated the phenotypes induced by Se deficiency or mutation of Trsp. Similarly, mutation of SelenoW in murine erythroblast (G1E) cells led to defects in terminal differentiation. In addition to the erythroid defects, the spleens of Se-deficient mice contained fewer red pulp macrophages and exhibited impaired development of erythroblastic island (EBI) macrophages, which make up the niche supporting erythroblast development. Taken together, these data reveal a critical role of selenoproteins in the expansion and development of stress erythroid progenitors as well as the erythroid niche during acute anemia recovery.

  • Submitted August 7, 2017.
  • Accepted March 15, 2018.