Research Group: Giampaolo Minetti, Annarita Ciana, Cesare Achilli

The production, aging, and clearance of red blood cells (RBCs) are the primary focuses of this research. Terminal erythropoiesis is the final step in producing mature RBCs. These non-nucleated cells in mammals lack most metabolic pathways and internal membranes and must complete their maturation from reticulocytes in circulation. Central to this process, as well as to RBC function, aging, and clearance, is the cell plasma membrane. Despite the wealth of information available on erythropoiesis and the composition and architecture of the RBC membrane—the most studied type of eukaryotic cell plasma membrane—the mechanistic details of terminal reticulocyte maturation remain unknown. Our group has made seminal contributions to understanding the red cell membrane organization, including the characterization of lipid rafts, the changes the membrane undergoes during in vivo and in vitro aging, and more recently, the discovery of significant changes in the lipid composition of the plasma membrane throughout the circulatory life of the RBC. Lipid reorganization in a cell type unable to perform de novo lipid biosynthesis has opened a new line of investigation into the mechanisms driving such changes. Lipid remodelling appears to be crucial, especially for the final steps in the maturation of a mechanically stable and functionally efficient cell envelope, enabling the cell to survive and perform its tasks efficiently in circulation for 120 days in humans. Our group has also made important contributions to understanding how erythropoiesis and cell clearance are regulated in hypoxia and microgravity. The results of this basic research will be essential for advancements in producing cultured RBCs for transfusion purposes, managing anaemia under various conditions, and better understanding rare diseases such as neuroacanthocytosis.

Recent Publications:

• Minetti G, Kaestner L, Köfeler H, Perotti C, Dorn I. Terminal maturation of human reticulocytes to red blood cells by extensive remodelling and progressive liquid ordering of membrane lipids. bioRxiv 2023.06.02.543386; DOI: https://doi.org/10.1101/2023.06.02.543386.
• Klein M, Kaestner L, Bogdanova AY, Minetti G, et al. Absence of neocytolysis in humans returning from a three-week high-altitude sojourn. Acta Physiol 2021;232:e13647. DOI: https://doi.org/10.1111/apha.13647.
• Minetti G, Achilli C, Perotti C, Ciana A. Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell. Front. Physiol. 2018;9:286. DOI: https://doi.org/10.3389/fphys.2018.00286.