Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation

Haruko Shima, Keiyo Takubo, Naoko Tago, Hiroko Iwasaki, Fumio Arai, Takao Takahashi, Toshio Suda

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1231-1240
Number of pages10
JournalExperimental Hematology
Volume38
Issue number12
DOIs
Publication statusPublished - 2010 Dec

Fingerprint

Hematopoietic Stem Cells
Bone Marrow Transplantation
Fetal Blood
Blood Cells
Cell Cycle
Bone Marrow
Hematopoietic Stem Cell Transplantation
Stem Cells
Transplantation
Cell Hypoxia
Interleukin-2 Receptors
Knockout Mice
Reverse Transcription
Leukemia
Maintenance
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation. / Shima, Haruko; Takubo, Keiyo; Tago, Naoko; Iwasaki, Hiroko; Arai, Fumio; Takahashi, Takao; Suda, Toshio.

In: Experimental Hematology, Vol. 38, No. 12, 12.2010, p. 1231-1240.

Research output: Contribution to journalArticle

Shima, Haruko ; Takubo, Keiyo ; Tago, Naoko ; Iwasaki, Hiroko ; Arai, Fumio ; Takahashi, Takao ; Suda, Toshio. / Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation. In: Experimental Hematology. 2010 ; Vol. 38, No. 12. pp. 1231-1240.
@article{9476f5673e834177bb5df7f3c4943937,
title = "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.",
author = "Haruko Shima and Keiyo Takubo and Naoko Tago and Hiroko Iwasaki and Fumio Arai and Takao Takahashi and Toshio Suda",
year = "2010",
month = "12",
doi = "10.1016/j.exphem.2010.08.004",
language = "English",
volume = "38",
pages = "1231--1240",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation

AU - Shima, Haruko

AU - Takubo, Keiyo

AU - Tago, Naoko

AU - Iwasaki, Hiroko

AU - Arai, Fumio

AU - Takahashi, Takao

AU - Suda, Toshio

PY - 2010/12

Y1 - 2010/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78549254160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78549254160&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2010.08.004

DO - 10.1016/j.exphem.2010.08.004

M3 - Article

VL - 38

SP - 1231

EP - 1240

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 12

ER -