Erythropoiesis in the absence of adult hemoglobin.

Mol Cell Biol

Department of Biochemistry and Molecular Genetics, University of Alabama, Birmingham, AL, USA.

Published: June 2013

During erythropoiesis, hemoglobin (Hb) synthesis increases from early progenitors to mature enucleated erythrocytes. Although Hb is one of the most extensively studied proteins, the role of Hb in erythroid lineage commitment, differentiation, and maturation remains unclear. In this study, we generate mouse embryos and embryonic stem (ES) cells with all of the adult α and β globin genes deleted (Hb Null). While Hb Null embryos die in midgestation, adult globin genes are not required for primitive or definitive erythroid lineage commitment. In vitro differentiation of Hb Null ES cells generates viable definitive proerythroblasts that undergo apoptosis upon terminal differentiation. Surprisingly, all stages of Hb Null-derived definitive erythroblasts develop normally in vivo in chimeric mice, and Hb Null erythroid cells undergo enucleation to form reticulocytes. Free heme toxicity is not observed in Hb Null-derived erythroblasts. Transplantation of Hb Null-derived bone marrow cells provides short-term radioprotection of lethally irradiated recipients, whose progressive anemia results in an erythroid hyperplasia composed entirely of Hb Null-derived erythroblasts. This novel experimental model system enables the role played by Hb in erythroid cell enucleation, cytoskeleton maturation, and heme and iron regulation to be studied.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648058PMC
http://dx.doi.org/10.1128/MCB.01734-12DOI Listing

Publication Analysis

Top Keywords

erythroid lineage
8
lineage commitment
8
adult globin
8
globin genes
8
null-derived erythroblasts
8
erythroid
5
erythropoiesis absence
4
absence adult
4
adult hemoglobin
4
hemoglobin erythropoiesis
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!