NDLI: The endothelial antigen ESAM monitors hematopoietic stem cell status between quiescence and self-renewal.

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The endothelial antigen ESAM monitors hematopoietic stem cell status between quiescence and self-renewal.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sudo, Takao Yokota, Takafumi Fujita, Natsuko Maeda, Tetsuo Nagasawa, Takashi Ishida, Tatsuro Oritani, Kenji Kanakura, Yuzuru Ezoe, Sachiko Sugiyama, Tatsuki Shibayama, Hirohiko Tanaka, Hirokazu Satoh, Yusuke
Description	Country affiliation: Japan Author Affiliation: Sudo T ( Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.)
Abstract	Whereas most hematopoietic stem cells (HSC) are quiescent in homeostasis, they actively proliferate in response to bone marrow (BM) injury. Signals from the BM microenvironment are thought to promote entry of HSC into the cell cycle. However, it has been cumbersome to assess cycle status of viable HSC and thus explore unique features associated with division. In this study, we show that expression of endothelial cell-selective adhesion molecule (ESAM) can be a powerful indicator of HSC activation. ESAM levels clearly mirrored the shift of HSC between quiescence and activation, and it was prominent in comparison with other HSC-related Ags. ESAM(hi) HSC were actively dividing, but had surprisingly high long-term reconstituting capacity. Immunohistochemical analyses showed that most ESAM(hi) HSC were located near vascular endothelium in the BM after 5-fluorouracil treatment. To determine the importance of ESAM in the process of BM recovery, ESAM knockout mice were treated with 5-fluorouracil and their hematopoietic reconstruction was examined. The ESAM deficiency caused severe and prolonged BM suppression, suggesting that ESAM is functionally indispensable for HSC to re-establish homeostatic hematopoiesis. With respect to intracellular regulators, NF-κB and topoisomerase II levels correlated with the ESAM upregulation. Thus, our data demonstrate that the intensity of ESAM expression is useful to trace activated HSC and to understand molecular events involved in stem cell states.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens Physiology Cell Adhesion Molecules Cell Differentiation Immunology Endothelium, Vascular Hematopoietic Stem Cells G0 Phase Animals Biosynthesis Genetics Biological Markers Metabolism Bone Marrow Cells Cytology Deficiency Cell Line Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Inbred Strains Mice, Knockout Comparative Study Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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