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
N1 - Funding Information:
This work was supported by Grants-in-Aid for Research for the Future Program from the Ministry of Education, Science, and Culture of Japan, by a Research Grant from Human Frontiers Science Program Organization, by a Takeda Science Foundation, by a Yamanouchi Foundation for Research on Metabolic Disorders, and by a Mitsubishi Pharma Research Foundation. We thank Dr. Mira Puri (University of Toronto) for critical reading of the manuscript. We acknowledge Dr. Naohiko Hayakawa (Chugai Pharmaceutical Co., Ltd.) for preparation of tissue sections of BM. We also thank Ms. Ayako Kumakubo and Ayami Ono for technical assistance. Authors dedicate this paper to the memory of Dr. Junko Suda who passed away during this work.
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
C2 - 15260986
AN - SCOPUS:3242669145
SN - 0092-8674
VL - 118
SP - 149
EP - 161
JO - Cell
JF - Cell
IS - 2
ER -