The regulation of lympho-hematopoiesis by bone marrow niches

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390096
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: NAGASAWA Takashi 京都大学, 再生医科学研究所, 教授 (80281690)
• Project Period (FY): 2010 – 2012
• Keywords: サイトカイン / 造血幹細胞

Research Abstract

We generated mice that allowed selective ablation of CAR cells within bone marrow and determined the in vivo function of CAR cells as a niche for hematopoietic stem cells (HSCs) and lympho-hematopoietic progenitors. Short-term ablation of CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells in vivo severely impaired the production of SCF and CXCL12, and led to a marked reduction in cycling lymphoid and erythroid progenitors. HSCs from CAR cell-depleted mice were reduced in number and cell size, were more quiescent and had increased expression of early myeloid selector genes. Thus, CAR cells are the major producer of CXCL12 and SCF and are required for proliferation of HSCs and lymphoid and erythroid progenitors as well as maintenance of HSCs in an undifferentiated state.

Research Products

• [Journal Article] CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance (2013)
  • Author(s): Greenbaum, A., Hsu, Y.M., Day, R.B., Schuettpel,z L.G., Christopher, M.J., Borgerding, J.N., Nagasawa, T., *Link, D.C.
  • Journal Title: Nature Volume: 495 Pages: 227-230
  • DOI: DOI:10.1038/nature11926
  • Peer Reviewed
• [Journal Article] Peripheral Nerve-Derived CXCL12 and VEGF-A Regulate the Patterning of Arterial Vessel Branching in Developing Limb Skin (2013)
  • Author(s): Li, W., Kohara, H., Uchida, Y., James, J.M., Soneji, K., Cronshaw, D.G., Zou, Y.R., Nagasawa, T., *Mukouyama, Y.S.
  • Journal Title: Dev. Cell Volume: Dev. Cell Pages: 359-371
  • DOI: DOI:10.1016/j.devcel.2013.01.009
  • Peer Reviewed
• [Journal Article] Reconstitution of mouse spermatogonial stem cell niches in culture. (2012)
  • Author(s): *Kanatsu-Shinohara, M., Inoue, K., Takashima, S., Takehashi, M., Ogonuki, N., Morimoto, H., Nagasawa, T., Ogura, A., Shinohara, T.
  • Journal Title: Cell Stem Cell Volume: 11 Pages: 567-578
  • DOI: DOI:10.1016/j.stem.2012.06.011
  • Peer Reviewed
• [Journal Article] Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system. (2012)
  • Author(s): Nishiyama, C., Uesaka, T., Manabe, T., Yonekura, Y., Nagasawa, T., Newgreen, D.F., Young, H.M., *Enomoto, H.
  • Journal Title: Nat. Neurosci. Volume: 15(9) Pages: 1211-1218
  • DOI: DOI:10.1038/nn.3184
  • Peer Reviewed
• [Journal Article] Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells. (2011)
  • Author(s): *Nagasawa, T., Omatsu, Y., Sugiyama, T
  • Journal Title: Trends Immunol Volume: 32(7) Pages: 315-320
  • DOI: DOI:10.1016/j.it.2011.03.009
  • Peer Reviewed
• [Journal Article] Emergency evacuation! Hematopoietic niches induce cell exit in infection. (2011)
  • Author(s): Sugiyama, T., *Nagasawa, T
  • Journal Title: Immunity Volume: 34(4) Pages: 463-465
  • DOI: DOI:10.1016/j.immuni.2011.04.009
  • Peer Reviewed
• [Journal Article] CXCL12-CXCR4 chemokine signaling is essential for NK cell development in adult mice. (2010)
  • Author(s): Noda, M., Omatsu, Y., Sugiyama, T., Oishi, S., Fujii, N., and *Nagasawa, T.
  • Journal Title: Blood Volume: 117 Pages: 451-458
  • DOI: DOI:10.1182/blood-2010-04-277897
  • Peer Reviewed
• [Journal Article] The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche. (2010)
  • Author(s): Omatsu,Y., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno, K., *Nagasawa, T
  • Journal Title: Immunity Volume: 33(3) Pages: 2010
  • DOI: DOI:10.1016/j.immuni.2010.08.017
  • Peer Reviewed
• [Presentation] Bone marrow niches controlling behavior of hematopoietic stem and progenitor cells (2012)
  • Author(s): T. Nagasaw
  • Organizer: The 21st Hot Spring Harbor Symposium jointly with 9th Global COE international Symposium; Cell Migration in Biology and Medicine
  • Place of Presentation: Fukuoka
  • Year and Date: 20120122-23
• [Presentation] Lymphocyte development "The adipo-osteogenic progenitors with long processes function as niches for hematopoietic stem and progenitor cells" (2012)
  • Author(s): T. Nagasawa
  • Organizer: 第41回日本免疫学会学術集会 シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Adipo-osteogenic progenitors function as niches for hematopoietic stem and progenitor cells in the marrow (2012)
  • Author(s): T. Nagasawa
  • Organizer: The 9th Nikko International Symposium 2012, Understanding complex network systems in disease biology.
  • Place of Presentation: Tochigi
  • Year and Date: 2012-10-12
• [Presentation] CXCL12 and reticular niches for hematopoietic stem and progenitor cells (2011)
  • Author(s): T. Nagasawa
  • Organizer: 40th Annual Scientific Meeting of the ISEH-Society for Hematology and Stem Cells, Break out session: Microenvironment.
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20110825-28
• [Presentation] Adipo-osteogenic progenitors constitute reticular niches for hematopoietic stem and progenitor cells (2011)
  • Author(s): T. Nagasawa
  • Organizer: The 23th Korean Society of Bone Metabolism Autumn Scientific Congress, Satellite Symposium:Bone and Hematopoietic System
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-11-19
• [Presentation] The chemokine CXCL12 and niches for hematopoietic stem cells and immune cells. (2010)
  • Author(s): T. Nagasawa
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 20100822-27
• [Presentation] The chemokine CXCL12 and bone marrow niches for HSCs and immune cells (2010)
  • Author(s): T. Nagasawa
  • Organizer: The 3rd International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems
  • Place of Presentation: Fira, Greece
  • Year and Date: 20100620-25