DOI: 10.1101/475905Nov 21, 2018Paper

Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo

BioRxiv : the Preprint Server for Biology
Hiroshi KobayashiKeiyo Takubo

Abstract

Hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis by remaining quiescent in the bone marrow niche. Recapitulation of a quiescent state in culture has not been achieved, as cells rapidly proliferate and differentiate in vitro. After exhaustive analysis of different environmental factor combinations and concentrations as a way to mimic physiological conditions, we were able to maintain engraftable quiescent HSCs for 1 month in culture under very low cytokine concentrations, hypoxia, and very high fatty acid levels. Exogenous fatty acids were required likely due to suppression of intrinsic fatty acid synthesis by hypoxia and low cytokine conditions. By contrast, high cytokine concentrations or normoxia induced HSC proliferation and differentiation. Our novel culture system provides a means to evaluate properties of steady state HSCs and test effects of defined factors in vitro under near-physiological conditions.

Related Concepts

Bone Marrow
Cell Differentiation Process
Environment
Fatty Acids
Hematopoiesis
Hematopoietic Stem Cells
Cytokine
Hypoxia
Expanded protein, Drosophila
Laboratory Culture

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