Speaker: Giulia Pavani, research associate in the Department of Pathology and Laboratory Medicine, Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia

Title: "Modeling human erythropoiesis during development"

Abstract: During development, erythroid cells are produced through at least two hematopoietic waves (primitive and definitive), which generate erythroblasts with different functional characteristics.

Induced pluripotent stem cells (iPSCs) can be differentiated into red blood cells (RBC) and help us model pathological and developmental processes that would otherwise be impossible to study in humans. While primitive erythropoiesis has been widely studied using iPSCs, definitive erythropoiesis has not been fully characterized as protocols that generate solely definitive with primitive hematopoietic progenitors were only recently described. To compare in vitro systems with human development, we generated iPSCs from a normal fetal liver sample, and produced iPSC-derived primitive and definitive red cells. Using scRNA-seq and functional assays, we could confirm a strong similarity between fetal liver and definitive iPSC-derived RBC, while primitive erythroblasts remained distinct. 

Our studies provide new insights into how the primitive and definitive programs differ regarding their transcriptome and highlight the importance of ontology when using iPSCs to model genetic hematologic diseases. Moreover, the generation of fetal liver-like erythroblasts further expand the potential applications of iPSC-derived RBC as diagnostic reagents and, eventually, transfusion products.

Host: Raquel Espin Palazon, genetics, development and cell biology assistant professor