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

Research output: Contribution to journalArticle

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 culture system provides a means to evaluate properties of steady-state HSCs and test effects of defined factors in vitro under near-physiological conditions. Maintaining quiescent HSCs under physiological conditions facilitates evaluation of the properties of steady-state HSCs. Kobayashi et al. report that low cytokine concentrations, hypoxia, and high fatty acid levels mimicking the bone marrow microenvironment enable maintenance of engraftable quiescent HSCs for 1 month in culture.

Original languageEnglish
Pages (from-to)145-158.e9
JournalCell Reports
Volume28
Issue number1
DOIs
Publication statusPublished - 2019 Jul 2

Fingerprint

Hematopoietic Stem Cells
Stem cells
Maintenance
Fatty Acids
Cell culture
Cytokines
Bone
Bone Marrow
Hematopoiesis
Cell proliferation
Cell Differentiation
Cell Proliferation
Hypoxia

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kobayashi, H., Morikawa, T., Okinaga, A., Hamano, F., Hashidate-Yoshida, T., Watanuki, S., ... Takubo, K. (2019). Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo. Cell Reports, 28(1), 145-158.e9. https://doi.org/10.1016/j.celrep.2019.06.008

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: Cell Reports, Vol. 28, No. 1, 02.07.2019, p. 145-158.e9.

Research output: Contribution to journalArticle

Kobayashi, H, Morikawa, T, Okinaga, A, Hamano, F, Hashidate-Yoshida, T, Watanuki, S, Hishikawa, D, Shindou, H, Arai, F, Kabe, Y, Suematsu, M, Shimizu, T & Takubo, K 2019, 'Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo', Cell Reports, vol. 28, no. 1, pp. 145-158.e9. https://doi.org/10.1016/j.celrep.2019.06.008
Kobayashi H, Morikawa T, Okinaga A, Hamano F, Hashidate-Yoshida T, Watanuki S et al. Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo. Cell Reports. 2019 Jul 2;28(1):145-158.e9. https://doi.org/10.1016/j.celrep.2019.06.008
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. / Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo. In: Cell Reports. 2019 ; Vol. 28, No. 1. pp. 145-158.e9.
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