Speaker: Sergei Doulatov, associate professor at University of Washington Institute for Stem Cell & Regenerative Medicine

Title: "Understanding hematopoietic stem cell function and progression to hematological malignancies through human iPSC models"

Abstract: Induced pluripotent stem cells (iPSCs) are a versatile model for understanding blood development in humans and modeling of hematological disorders. During ontogeny, hematopoietic stem and progenitor cells (HSPCs) arise from specialized arterial hemogenic endothelium through a process called endothelial to hematopoietic transition (EHT). We have generated a single cell map of EHT during iPSC differentiation identifying key regulators of EHT in humans. During postnatal life, HSPCs evolve through acquisition of somatic mutations giving rise to clonal hematopoiesis and hematological malignancies. We have used iPSC reprogramming to model clonal evolution and develop disease models. Splicing factor mutations are found in nearly half of patients with blood malignancies. I will discuss our recent work on understanding how splicing factor mutations reshape the transcriptome and function of HSPCs by promoting coordinated mis-splicing of genes in specific biological pathways.

Hosts: Clyde Campbell, genetics, development and cell biology (GDCB) adjunct assistant professor; and Raquel Espin Palazon, GDCB assistant professor