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876 Combined Single-Cell and Spatial Transcriptomics to Deconvolute the Hematopoietic Stem Cell Niche

Program: Oral and Poster Abstracts
Type: Oral
Session: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells
Hematology Disease Topics & Pathways:
Biological Processes, cellular interactions, Technology and Procedures, genomics, hematopoiesis, RNA sequencing, multi-systemic interactions
Monday, December 3, 2018: 5:45 PM
Grand Hall D (Manchester Grand Hyatt San Diego)

Simon Haas, PhD1*, Chiara Baccin2*, Jude Al-Sabah3*, Lars Velten, PhD2*, Steinmetz Lars, PhD4* and Andreas Trumpp, Prof, PhD5

1German Cancer Research Centre (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) ; Division of Stem Cells and Cancer, Heidelberg, Germany
2EMBL, Heidelberg, Germany
3DKFZ / HI-STEM gGmbH, Heidelberg, Germany
4EMBL & Stanford, Heidelberg, Germany
5German Cancer Research Center (DKFZ) / HI-STEM, Heidelberg, Germany

Coordinated interaction of many cell types is required to facilitate hematopoietic and mesenchymal stem cell maintenance and differentiation in the bone marrow. However, the molecular factors and cell types involved in this complex interplay remain poorly understood. Here we developed a combined single cell and spatial transcriptomics approach to address this problem.

Large-scale single-cell transcriptional profiling in conjunction with a multi-layered sorting approach allowed us to generate a complete and evenly sampled transcriptional map of all major bone and bone marrow populations. Our dataset covers all cell types or differentiation trajectories involved in mesenchymal and hematopoietic stem cell differentiation, osteogenesis, adipogenesis, myelopoiesis, erythropoiesis, lymphopoiesis, memory T cell formation as well as bone marrow neural innervation and vascularization at the single cell level. Using this data, we derive fundamental properties of the described cell types, clarify the cellular source of signals affecting stem cell differentiation processes and provide a systems view on putative intercellular interactions. Systematic spatial transcriptomics, using laser-capture microdissection of selected bone marrow niches followed by transcriptional profiling and bioinformatic cellular deconvolution, allowed us to confirm predicted interactions and map the cellular composition of distinct bone marrow niches.

Our analyses highlight the importance of pre-adipogenic CXCL12 abundant reticular cells as key niche cells for stem cell maintenance, provides a holistic systems view of the hematopoietic stem cell niche and offers a novel approach to systematically deconvolute the molecular, cellular and spatial composition of complex tissues.

Disclosures: No relevant conflicts of interest to declare.

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