Integrative Proteome and Transcriptome Analysis of Extramedullary Erythropoiesis and Its Reversal by Transferrin Treatment in a Mouse Model of Beta-Thalassemia

Beta-thalassemia
results from mutations of the β-hemoglobin
(Hbb) gene and reduced functional Hbb synthesis. Excess α-Hb
causes globin chain aggregation, oxidation, cytoskeletal damage, and
increased red blood cell clearance. These events result in anemia,
altered iron homeostasis, and expansion of extramedullary erythropoiesis.
Serum transferrin (Tf) is suggested to be an important regulator of
erythropoiesis in murine models of thalassemia. The present study
was conducted to establish a quantitative proteomic and transcriptomic
analysis of transferrin-modulated extramedullary erythropoiesis in
the spleen of wild type and thalassemic Hbbth3/+ mice.
Our LC-MS/MS protein analysis and mRNA sequencing data provide quantitative
expression estimates of 1590 proteins and 24 581 transcripts
of the murine spleen and characterize key processes of erythropoiesis
and RBC homeostasis such as the whole heme synthesis pathway as well
as critical components of the red blood cell antioxidant systems and
the proliferative cell cycling pathway. The data confirm that Tf treatment
of nontransfused Hbbth3/+ mice induces a systematic correction
of these processes at a molecular level. Tf treatment of Hbbth3/+ mice for 60 days leads to a complete molecular restoration of the
normal murine spleen phenotype. These findings support further investigation
of plasma-derived Tf as a treatment for thalassemia.