CRISPR Edited Megakaryocytes for Rapid Screening of Platelet Gene Functions

Emilie Montenont, Ph.D.
The University of Utah
Salt Lake City, U.S.

Achieving consistent genetic modifications in primary megakaryocytes has been challenging, as the functional effects on human megakaryocytes of induced gene deletions for even well-studied platelet genes are unknown. Emilie Montenont, Ph.D., of The University of Utah commented that the goal of her research was to develop and define the strengths and limitations of a rapid and systematic approach to screen genes for platelet functions in primary megakaryocytes called CRIMSON. The results were presented at the ISTH 2021 Virtual Congress on Monday, July 19, 2021.

Using microscopy and flow cytometry analysis to assess platelet-like functional responses in megakaryocytes, Montenont presented via CRIMSON, gene editing induced a loss of protein in up to 98% of cells for platelet function genes glycoprotein VI (GP6), RAS guanyl-releasing protein-2 (RASGRP2), and integrin subunit alpha 2b (ITGA2B). Gene deletions affected several responses to platelet agonists in megakaryocytes in a manner largely consistent with those expected for platelets. Observations following CRIMSON can also identify subtle to severe phenotypes, leading the way for systematic identification of novel genes involved in platelet function. Watch and learn from the excitement that Montenont shared regarding these and additional results, as CRIMSON is suggested for use in the rapid evaluation of platelet gene phenotype associations.