Abstract 4497: A single-cell multiomics approach to study tumor-driven perturbations during hematopoiesis in mice

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 (MDSCs), tumor associated macrophages (TAMs) and neutrophils (TANs). These myeloid derived cells are known to modulate immune responses that enhance cancer cell stemness, angiogenesis, metastasis, invasion and immune escape. The prevailing paradigm is that cancer interferes with hematopoiesis and skews the host system to generate cells of myeloid origin with tumor-promoting functions. Intriguingly, tumor derived factors can perturbate normal bone marrow hematopoiesis and promote 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 four hematopoietic stem and progenitor cell populations simultaneously, including Lin- Sca-1+ c-Kit+ (LSK), common myeloid progenitor (CMP), granulocyte-macrophage progenitor (GMP) and megakaryocyte-erythrocyte progenitor (MEP) 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. Not for use in diagnostic or therapeutic procedures. 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. Citation Format: Nihan Kara, Xiaoshan Shi, Nikolay Samusik, Stephanie Widmann, Aaron J. Tyznik. A single-cell multiomics approach to study tumor-driven perturbations during hematopoiesis in mice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4497.

Multiomics uncovers developing immunological lineages in human

“…Newer techniques, such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE‐seq) [ 20 ], BD Rhapsody [ 21 , 22 ], RNA expression and protein sequencing assay (REAP‐seq) [ 23 ], and PrimeFlow [ 24 ] are now able to acquire both transcript and protein data from a single cell. CITE‐seq, for example, provides a digital readout of cell surface proteins by using antibody‐oligo conjugates [ 20 ].…”