Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation
Abstract
Objective Hematopoietic stem cells are kept in a quiescent state in the hypoxic area of the bone marrow, which is essential for hematopoietic stem cell maintenance. However, when and how hematopoietic stem cells acquire their hypoxic state and maintain quiescence has not been fully elucidated. The aim of this study was to understand this process in human hematopoietic stem cells after bone marrow transplantation.Materials and methods Human CD34-positive cord blood cells were transplanted into nonobese diabetic/severe combined immunodeficient interleukin-2 receptor γ chain knockout mice. Cell cycle and hypoxia assay analyses were performed, to identify changes in the characteristics of human hematopoietic stem cells following transplantation. Quantitative real-time reverse transcription polymerase chain reaction analysis was used to analyze the transcriptional changes accompanying this transition.Results Engrafted primitive lineage-negative CD34-positive CD38-negative cells acquired hypoxic state and quiescence in the recipient bone marrow between 4 and 8 weeks, and between 8 and 12 weeks after transplantation, respectively. During 4 and 8 weeks after transplantation, changes in the transcription levels of G₀ regulatory factors, such as CCNC and RBL1, and stem cell regulators, such as Flt3, were also seen, which may be related to the characteristic changes in the cell cycle or oxygenation state.Conclusions Behavioral changes of hematopoietic stem cells in their cell cycle and oxygenation state during and after bone marrow engraftment may provide insights into hematopoietic stem cell regulation, mediating the improvement of clinical hematopoietic stem cell transplantation protocols and the eradication of leukemia stem cells.
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Quiescence is induced when cultured haematopoietic cells are grown under hypoxic conditions.
“quiescence is induced when cultured haematopoietic cells are grown under hypoxic conditions113,114.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [113]
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- Authors
- Shima, H., Takubo, K., Tago, N., Iwasaki, H., Arai, F., Takahashi, T., & Suda, T.
- Affiliations
- Keio University (JP)
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 38
- Issue
- 12
- Pages
- 1231-1240
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W2125868380
- Cited by
- 35
- References
- 49
- Citations by year
- 2024: 2 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 7 · 2012: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- hematopoietic stem cells, G0 quiescence, hypoxia, bone marrow transplantation, cord blood cells, CD34+ cells, cell cycle, hematopoietic stem cell maintenance, CCNC, RBL1, FLT3, engraftment
- MeSH terms
- Animals, Female, Fetal Blood, Hematopoietic Stem Cells, Humans, Bone Marrow Transplantation, Resting Phase, Cell Cycle, Hematopoietic Stem Cell Transplantation, Antigens, CD34, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, fms-Like Tyrosine Kinase 3, ADP-ribosyl Cyclase 1
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