Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche |
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Authors: | Kubota Yoshiaki Takubo Keiyo Suda Toshio |
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Affiliation: | Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan |
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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. |
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Keywords: | Hematopoietic stem cell Sinusoid Hypoxia Osteoblastic niche Vascular niche Hypoxic niche Sinusoidal niche Quiescence Label-retaining cell c-kit |
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