A single-cell multiomics approach to study tumor-driven perturbations during hematopoiesis in mice

Abstract

Abstract Cancer is associated with concomitant myeloid cell responses that are characterized by an expansion of tumor associated myeloid cells, including myeloid derived suppressor cells, tumor associated macrophages and neutrophils. The prevailing paradigm is that cancer interferes with normal hematopoiesis by skewing the generation of myeloid cells with tumor promoting functions and promoting extramedullary hematopoiesis in organs such as the spleen. Advances in single cell multiomic technologies now enable the analysis of high dimensional protein and mRNA expression from thousands of cells simultaneously. Using the power of the BD Rhapsody™ Single-Cell Analysis System, we have carefully investigated melanoma associated extramedullary hematopoiesis in mice. To do this, we isolated 4 hematopoietic stem and progenitor cell populations simultaneously, including Lin− Sca-1+ c-Kit+, common myeloid progenitor, granulocyte-macrophage progenitor, and megakaryocyte-erythrocyte progenitor cells from the spleen and bone marrow of melanoma bearing mice using the BD FACSMelody™ cell sorter in combination with a multiplex BD® AbSeq Oligos panel for surface protein expression and a single-cell whole transcriptome analysis. Using advanced analysis plugins in SeqGeq™ software, we were able to delineate the developmental trajectories of these hematopoietic stem and progenitor cells in this systemic immuno-suppressive myeloid environment. These advanced technologies are critical to uncover tumor mediated abnormalities in hematopoiesis. Disclaimers: For Research Use Only. Class 1 Laser Product. BD, the BD Logo, FACSMelody and Rhapsody are trademarks of Becton, Dickinson and Company or its affiliates. © 2019 BD. All rights reserved.