Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo

Hiroshi Kobayashi; Takayuki Morikawa; Ayumi Okinaga; Fumie Hamano; Tomomi Hashidate-Yoshida; Shintaro Watanuki; Daisuke Hishikawa; Hideo Shindou; Fumio Arai; Yasuaki Kabe; Makoto Suematsu; Takao Shimizu; Keiyo Takubo

doi:10.1101/475905

Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo

Hiroshi Kobayashi, Takayuki Morikawa, Ayumi Okinaga, Fumie Hamano, Tomomi Hashidate-Yoshida, Shintaro Watanuki, Daisuke Hishikawa, Hideo Shindou, Fumio Arai, Yasuaki Kabe, Makoto Suematsu, Takao Shimizu, Keiyo Takubo

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/475905
Publication status	Published - 2018 Nov 21

Keywords

fatty acid
hematopoietic stem cell
hypoxia
stem cell culture
stem cell metabolism
stem cell niche

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo. / Kobayashi, Hiroshi; Morikawa, Takayuki; Okinaga, Ayumi; Hamano, Fumie; Hashidate-Yoshida, Tomomi; Watanuki, Shintaro; Hishikawa, Daisuke; Shindou, Hideo; Arai, Fumio; Kabe, Yasuaki ; Suematsu, Makoto; Shimizu, Takao; Takubo, Keiyo.

In: Unknown Journal, 21.11.2018.

Research output: Contribution to journal › Article › peer-review

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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.",

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author = "Hiroshi Kobayashi and Takayuki Morikawa and Ayumi Okinaga and Fumie Hamano and Tomomi Hashidate-Yoshida and Shintaro Watanuki and Daisuke Hishikawa and Hideo Shindou and Fumio Arai and Yasuaki Kabe and Makoto Suematsu and Takao Shimizu and Keiyo Takubo",

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AU - Hashidate-Yoshida, Tomomi

AU - Watanuki, Shintaro

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AU - Shindou, Hideo

AU - Arai, Fumio

AU - Kabe, Yasuaki

AU - Suematsu, Makoto

AU - Shimizu, Takao

AU - Takubo, Keiyo

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/11/21

Y1 - 2018/11/21

N2 - 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.

AB - 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.

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