Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo
Summary: 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 environmenta...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-07-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307661 |
| _version_ | 1818312557060947968 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Hiroshi Kobayashi |
| collection | DOAJ |
| description | Summary: 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. Keywords: hematopoietic stem cell, stem cell culture, stem cell metabolism, fatty acid, hypoxia, stem cell niche, quiescence |
| first_indexed | 2024-12-13T08:19:44Z |
| format | Article |
| id | doaj.art-0d5b7262cdce4be7b9a78ccf3be0990f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T08:19:44Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0d5b7262cdce4be7b9a78ccf3be0990f2022-12-21T23:54:02ZengElsevierCell Reports2211-12472019-07-01281145158.e9Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex VivoHiroshi Kobayashi0Takayuki Morikawa1Ayumi Okinaga2Fumie Hamano3Tomomi Hashidate-Yoshida4Shintaro Watanuki5Daisuke Hishikawa6Hideo Shindou7Fumio Arai8Yasuaki Kabe9Makoto Suematsu10Takao Shimizu11Keiyo Takubo12Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, JapanDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; Department of Lipid Science, Graduate School of Medicine, The University of Tokyo, 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; Corresponding authorSummary: 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. Keywords: hematopoietic stem cell, stem cell culture, stem cell metabolism, fatty acid, hypoxia, stem cell niche, quiescencehttp://www.sciencedirect.com/science/article/pii/S2211124719307661 |
| spellingShingle | 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 Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo Cell Reports |
| title | Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo |
| title_full | Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo |
| title_fullStr | Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo |
| title_full_unstemmed | Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo |
| title_short | Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo |
| title_sort | environmental optimization enables maintenance of quiescent hematopoietic stem cells ex vivo |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307661 |
| work_keys_str_mv | AT hiroshikobayashi environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT takayukimorikawa environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT ayumiokinaga environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT fumiehamano environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT tomomihashidateyoshida environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT shintarowatanuki environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT daisukehishikawa environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT hideoshindou environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT fumioarai environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT yasuakikabe environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT makotosuematsu environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT takaoshimizu environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo AT keiyotakubo environmentaloptimizationenablesmaintenanceofquiescenthematopoieticstemcellsexvivo |