title: Integrative proteome and transcriptome analysis of extramedullary erythropoiesis and its reversal by transferrin treatment in a mouse model of beta-thalassemia.
abstract: 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 Hbb(th3/+) 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 Hbb(th3/+) mice induces a systematic correction of these processes at a molecular level. Tf treatment of Hbb(th3/+) 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.
authors.affiliation: Division of Internal Medicine, University of Zurich , CH-8091 Zurich, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Vallelian
authors.forename: Monique P
authors.initials: MP
authors.lastname: Gelderman-Fuhrmann
authors.forename: Christian A
authors.initials: CA
authors.lastname: Schaer
authors.forename: Michele
authors.initials: M
authors.lastname: Puglia
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Jin Hyen
authors.initials: JH
authors.lastname: Baek
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Vostal
authors.forename: Paul W
authors.initials: PW
authors.lastname: Buehler
authors.forename: Dominik J
authors.initials: DJ
authors.lastname: Schaer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004920:Erythropoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome; D059467:Transcriptome; D014168:Transferrin / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D020543:Proteome; D014168:Transferrin
keywords: LC-MSMS; anemia; erythropoiesis; mRNA sequencing; spleen; thalassemia; therapy; transferrin