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Blood. 2019 Oct 10;134(15):1214-1226. doi: 10.1182/blood.2019000176.

Prospective isolation of nonhematopoietic cells of the niche and their differential molecular interactions with HSCs.

Author information

1
Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology Medical Faculty, Technische Universität (TU) Dresden, Dresden, Germany.
2
Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.
3
Regeneration in Hematopoiesis, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
4
Stem Cell Engineering, Biotechnology Center, BioInnovationsZentrum, TU Dresden, Dresden, Germany.
5
Medical Clinic for Internal Medicine III, Klinikum Rechts der Isar, TU München, Munich, Germany.
6
Dresden-Concept Genome Center, c/o Center for Molecular and Cellular Bioengineering (CMCB), and.
7
Department of Medicine III, TU Dresden, Dresden, Germany; and.
8
Faculty of Biological Sciences, Friedrich Schiller University Jena, Jena, Germany.

Abstract

A major limitation preventing in vivo modulation of hematopoietic stem cells (HSCs) is the incomplete understanding of the cellular and molecular support of the microenvironment in regulating HSC fate decisions. Consequently, murine HSCs cannot be generated, maintained, or expanded in culture over extended periods of time. A significantly improved understanding of the bone marrow niche environment and its molecular interactions with HSCs is pivotal to overcoming this challenge. We here prospectively isolated all major nonhematopoietic cellular niche components and cross-correlate them in detail with niche cells defined by lineage marking or tracing. Compiling an extensive database of soluble and membrane-bound ligand-receptor interactions, we developed a computational method to infer potential cell-to-cell interactions based on transcriptome data of sorter-purified niche cells and hematopoietic stem and progenitor cell subpopulations. Thus, we establish a compendium of the molecular communication between defined niche components and HSCs. Our analysis suggests an important role for cytokine antagonists in the regulation of HSC functions.

PMID:
31366622
DOI:
10.1182/blood.2019000176

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