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Title: Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche

Abstract

In response to changing signals, quiescent hematopoietic stem cells (HSCs) can be induced to an activated cycling state and provide multi-lineage hematopoietic cells to the whole body via blood vessels. However, the precise localization of quiescent HSCs in bone marrow microenvironment is not fully characterized. Here, we performed whole-mount immunostaining of bone marrow and found that BrdU label-retaining cells (LRCs) definitively reside in the sinusoidal hypoxic zone distant from the 'vascular niche'. Although LRCs expressed very low level of a well-known HSC marker, c-kit in normal circumstances, myeloablation by 5-FU treatment caused LRCs to abundantly express c-kit and proliferate actively. These results demonstrate that bone marrow LRCs reside in the sinusoidal hypoxic niche, and function as a regenerative cell pool of HSCs.

Authors:
;  [1];  [2]
  1. Department of Cell Differentiation, Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)
  2. Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan), E-mail: sudato@sc.itc.keio.ac.jp
Publication Date:
OSTI Identifier:
21043610
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 366; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2007.11.086; PII: S0006-291X(07)02480-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; BLOOD VESSELS; BONE MARROW; STEM CELLS

Citation Formats

Kubota, Yoshiaki, Takubo, Keiyo, and Suda, Toshio. Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2007.11.086.
Kubota, Yoshiaki, Takubo, Keiyo, & Suda, Toshio. Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche. United States. doi:10.1016/j.bbrc.2007.11.086.
Kubota, Yoshiaki, Takubo, Keiyo, and Suda, Toshio. 2008. "Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche". United States. doi:10.1016/j.bbrc.2007.11.086.
@article{osti_21043610,
title = {Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche},
author = {Kubota, Yoshiaki and Takubo, Keiyo and Suda, Toshio},
abstractNote = {In response to changing signals, quiescent hematopoietic stem cells (HSCs) can be induced to an activated cycling state and provide multi-lineage hematopoietic cells to the whole body via blood vessels. However, the precise localization of quiescent HSCs in bone marrow microenvironment is not fully characterized. Here, we performed whole-mount immunostaining of bone marrow and found that BrdU label-retaining cells (LRCs) definitively reside in the sinusoidal hypoxic zone distant from the 'vascular niche'. Although LRCs expressed very low level of a well-known HSC marker, c-kit in normal circumstances, myeloablation by 5-FU treatment caused LRCs to abundantly express c-kit and proliferate actively. These results demonstrate that bone marrow LRCs reside in the sinusoidal hypoxic niche, and function as a regenerative cell pool of HSCs.},
doi = {10.1016/j.bbrc.2007.11.086},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 366,
place = {United States},
year = 2008,
month = 2
}
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