Description:
Erythropoiesis is a complex carefully orchestrated process that replenishes billions of erythrocytes lost daily.  Producing red blood cells at large scale is a major clinical need. Challenges encountered in producing red blood cells in vitro for clinical use, have highlighted the necessity to better understand processes involved. The molecular mechanisms involved in erythroid differentiation are tightly regulated and compartmentalized in erythroid precursors. In this session, speakers will discuss their work using new technology, including super resolution microscopy to dissect at nanoscale the compartmentalization of proteins or organelles, cytoskeletal rearrangement and erythroid enucleation to better understand red blood cell generation. Another topic addressed will be the overall production of red blood cells from reprogrammed fibroblasts in vitro for clinical use.

Dr. Ke Xu will discuss the importance of using super-resolution fluorescence microscopy to understand the ultrastructure of red cells. Recent advances in super-resolution fluorescence microscopy offers exciting new opportunities to probe intracellular structures at ~20 nm resolution with excellent molecular specificity and minimal sample processing. This presentation will shed new light on related cytoskeletal systems in erythropoiesis. Super-resolution fluorescence microscopy opens a new window into understanding the ultrastructure of red cells, and the impact these methods have on our understating of erythroid differentiation will be discussed.

Dr. Johan Flygare will discuss the background and clinical significance of understanding transcriptional programs regulating the developmental waves of erythropoiesis. He will focus less on what has been learned from loss of function approaches and instead highlight overexpression approaches being used to study key transcription factors in erythropoiesis. Dr. Flygare will include published and unpublished results from his own studies using direct lineage reprogramming from fibroblasts to erythroid progenitor cells and will finish with future perspectives.

Dr. Velia Fowler will discuss how the biogenesis of mammalian red blood cells is a highly orchestrated process of terminal differentiation with a series of cell divisions coupled to dramatic changes in cell and nuclear morphology, culminate in cell cycle exit and nuclear expulsion (enucleation).  While enucleation has been assumed to be a type of asymmetric cell division, differences in cell polarity control and nanoscale organization of cytoskeletal structures indicate otherwise.  The molecular and structural basis for events of enucleation will be discussed and evaluated critically, with an eye on providing strategies for optimizing red cell production in vitro.