Platelets have important roles in not only hemostasis but also other key biological and pathological processes such as immunoregulation, malignancy, angiogenesis, and wound healing. Historically, megakaryocytes have been considered a phenotypically homogenous population that produce a uniform population of platelets. However, recent studies have challenged this paradigm and created a fundamental shift in how we view both megakaryocytes and their platelet progeny. This session will focus on heterogeneity in the development and function of platelets and their precursor cells, megakaryocytes.

Dr. Krause will present cell and molecular insights into the fate specification of primary human megakaryocytic-erythroid progenitors (MEP). While much is known about how megakaryoblasts and erythroblasts progress to maturation, the signaling, transcriptomic, and epigenetic changes that occur during MEP fate specification are still largely unknown. Dr. Krause will present data revealing roles for differential transcription, epigenetics and the cell cycle in MEP fate specification based on functional assays and high throughput molecular approaches as well as recently published timelapse microscopy studies.

Dr. Alastair Poole will present evidence showing emergence of megakaryocytes into vasculature including an in vitro heart-lung system that has been developed to allow perfusion of megakaryocytes through the pulmonary vasculature. High efficiency of in vitro platelet generation in lung vasculature is shown and demonstration that in vitro microfluidic chambers mimic this vasculature, enabling large scale functional platelet generation in vitro.

Dr. Anandi Krishnan will discuss how platelet transcriptomic signatures not only capture information from parent megakaryocytes and progenitor hematopoietic stem cells but also underlying disease states. In cancer, substantive body of research in patients with solid tumors have identified distinct signatures in ‘tumor educated platelets’, reflecting influences of the tumor, stroma and vasculature on splicing, sequestration of tumor-derived RNAs and potentially cytokine and microvesicle influences on megakaryocytes. Dr. Krishnan’s lab has identified platelet RNA expression as a highly sensitive approach to profiling chronic progressive hematologic malignancies, where the combination of large data cohorts and machine-learning algorithms enable precise feature selection and potential prognostication. This talk will also highlight actionable steps required toward advancing the utility of the platelet transcriptome as a highly sensitive biomarker in cancer and emphasize the immense opportunities for personalized medicine.