Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche

Fumio Arai, Atsushi Hirao, Masako Ohmura, Hidetaka Sato, Sahoko Matsuoka, Keiyo Takubo, Keisuke Ito, Gou Young Koh, Toshio Suda

Research output: Contribution to journalArticle

1346 Citations (Scopus)

Abstract

The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.

Original languageEnglish
Pages (from-to)149-161
Number of pages13
JournalCell
Volume118
Issue number2
DOIs
Publication statusPublished - 2004 Jul 23

Fingerprint

Angiopoietin-1
Hematopoietic Stem Cells
Stem cells
Bone
Bone Marrow
Maintenance
Stem Cell Niche
Hematopoiesis
Receptor Protein-Tyrosine Kinases
Osteoblasts
Adhesion
Ligands
Bone and Bones

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., ... Suda, T. (2004). Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell, 118(2), 149-161. https://doi.org/10.1016/j.cell.2004.07.004

Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. / Arai, Fumio; Hirao, Atsushi; Ohmura, Masako; Sato, Hidetaka; Matsuoka, Sahoko; Takubo, Keiyo; Ito, Keisuke; Koh, Gou Young; Suda, Toshio.

In: Cell, Vol. 118, No. 2, 23.07.2004, p. 149-161.

Research output: Contribution to journalArticle

Arai, F, Hirao, A, Ohmura, M, Sato, H, Matsuoka, S, Takubo, K, Ito, K, Koh, GY & Suda, T 2004, 'Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche', Cell, vol. 118, no. 2, pp. 149-161. https://doi.org/10.1016/j.cell.2004.07.004
Arai, Fumio ; Hirao, Atsushi ; Ohmura, Masako ; Sato, Hidetaka ; Matsuoka, Sahoko ; Takubo, Keiyo ; Ito, Keisuke ; Koh, Gou Young ; Suda, Toshio. / Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. In: Cell. 2004 ; Vol. 118, No. 2. pp. 149-161.
@article{fcc4d023332d44d19007f25ec370fe6f,
title = "Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche",
abstract = "The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.",
author = "Fumio Arai and Atsushi Hirao and Masako Ohmura and Hidetaka Sato and Sahoko Matsuoka and Keiyo Takubo and Keisuke Ito and Koh, {Gou Young} and Toshio Suda",
year = "2004",
month = "7",
day = "23",
doi = "10.1016/j.cell.2004.07.004",
language = "English",
volume = "118",
pages = "149--161",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche

AU - Arai, Fumio

AU - Hirao, Atsushi

AU - Ohmura, Masako

AU - Sato, Hidetaka

AU - Matsuoka, Sahoko

AU - Takubo, Keiyo

AU - Ito, Keisuke

AU - Koh, Gou Young

AU - Suda, Toshio

PY - 2004/7/23

Y1 - 2004/7/23

N2 - The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.

AB - The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.

UR - http://www.scopus.com/inward/record.url?scp=3242669145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242669145&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.07.004

DO - 10.1016/j.cell.2004.07.004

M3 - Article

VL - 118

SP - 149

EP - 161

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -