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 - Institute for Frontier Medical Sciences
Immunobiology and Hematology
Field of Biological Function
To understand the mechanisms regulating temporal and spatial generation of stem and progenitor cells within organs, we focus our analysis on microenvironmental niches for hematopoietic stem cells (HSCs) and progenitors and requisite signals provided by the niches, including the chemokine CXCL12 (SDF-1) and its receptor CXCR4. We utilize various techniques based on molecular biology, cellular biology, developmental biology and histology. The students are trained to be an excellent scientist, doing the research with us.

  Takashi Nagasawa, M.D., Ph.D.
Professor
Research and Education
Chemokines are a large family of small structurally related cytokines that are thought to regulate cell trafficking and utilize seven- transmembrane spanning G-protein-coupled receptors (GPCR). We identified CXC chemokine ligand 12 (CXCL12), also known as stromal cell-derived factor (SDF)-1 as pre-B-cell growth stimulating factor and found that CXCL12 and its primary receptor CXCR4 are essential for hematopoiesis, including colonization of bone marrow by hematopoietic stem cells (HSCs) during ontogeny, maintenance of the HSC pool in adult bone marrow and development of B lymphocytes and plasmacytoid dendritic cells (pDCs) as well as cardiogenesis and organ vasculalization during ontogeny (4,5). Recently, we have identified a small population of non-hematopoietic cells expressing high amounts of CXCL12, termed CXCL12-abundant reticular (CAR) cells with long processes. We have revealed that CAR cells are scattered throughout bone marrow and that most HSCs, early B cell precursors, the end-stage B lymphocyte plasma cells and pDCs are attached to the processes of CAR cells and that CAR cells are adipo-osteogenic progenitors, which function as the special microenvironments, termed ‘niches’ for HSCs and hematopoietic progenitors (1-3). We educate students in research, reading of papers and discussion.


Immunobiology and Hematology
Institute for Frontier Medical Sciences
Professor Takashi Nagasawa
Assistant
 Professor


Tatsuki Sugiyama
TEL +81-75-751-4100
FAX +81-75-751-4820
e-mail tnagasafrontier.kyoto-u.ac.jp
URL http://www.frontier.kyoto-u.ac.jp/se03/index-e.html
CXCL12-CXCR4 signaling is essential for homing of HSCs and primordal germ cells (PGCs) to the bone marrow and gonads, respectively during ontogeny and might be involved in cancer metastasis, colonization of cancer stem cells in the adult.
CAR cells, expressing high levels of CXCL12 have long processes.
Model of niches for HSCs and lympho-hematopoietic cells.
Laboratory members.
Recent Publications
1. Omatsu, T., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno,, K., *Nagasawa, T. The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche.
Immunity 33; 387-399, 2010.
2. Sugiyama, T., Kohara, H., Noda, M., and *Nagasawa, T. Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Signaling in Bone Marrow Stromal Cell Niches.
Immunity 25; 977-988. 2006.
3. Tokoyoda, K., Egawa, T., Sugiyama, T., Byung-I1 Choi and *Nagasawa, T. Cellular niches controlling B lymphocyte behavior within bone marrow during development.
Immunity 20; 707-718, 2004
4. Tachibana, K., Hirota, S., Iizasa, H., Yoshida, H., Kawabata, K., Kataoka, Y., Kitamura, Y., Matsushima, K., Yoshida, N., Nishikawa, S., Kishimoto, T., and *Nagasawa, T. The chomokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
Nature 393: 591-594, 1998.
5. *Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S.-I., Kitamura, Y.,Yoshida, N., Kikutani, H., and Kishimoto, T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.
Nature 382: 635-638, 1996