December 2014 CXCL12-abundant reticular cells as a microenvironmental niche in bone marrow


CXCL12-abundant reticular cells as

a microenvironmental niche in bone marrow

B6;129P2-Cxcl12<tm2Tng>/TngRbrc (RBRC04200)
B6;129P2-Cxcr4<tm2Tng>/TngRbrc (RBRC04198)


Courtesy of Takashi Nagasawa, M.D., Ph.D.

Cell bodies and processes of CXCL12-abundant reticular (CAR) cells, which create a niche for hematopoietic stem and progenitor cells (HSPCs), can be observed in the bone marrow of CXCL12-GFP knock-in mice.

CXC chemokine ligand 12 (CXCL12), also known as stromal cell-derived factor (SDF)-1 or pre-B cell growth-stimulating factor (PBSF) was characterized initially as a growth factor for B cell precursor clones. CXCL12 stimulation is mediated by the G protein-coupled receptor CXCR4. Studies using conventional and conditional knockout mice revealed that CXCL12-CXCR4 signaling has an essential role in hematopoietic stem cell (HSC) maintenance, B cell and germ cell development, neurogenesis, cardiogenesis, and vascular formation [1-4]. Nagasawa and colleagues have revealed the role of CXCL12-abundant reticular (CAR) cells, which are a population of stromal cells that are scattered throughout bone marrow and express high levels of CXCL12 [5, 6]. Recently, they determined a critical role for CAR cells as a microenvironmental niche for HSCs and lymphoid and erythroid progenitors [7-9]. Analyses of CXCL12-CXCR4 signaling in vivo will clarify the molecular mechanisms underlying microenvironmental niche formation in mammals.


Depositor : Takashi Nagasawa, M.D., Ph.D.
Department of Immunobiology and Hematology
Institute for Frontier Medical Sciences, Kyoto University
Strain name : B6;129P2-Cxcl12<tm2Tng>/TngRbrc
RBRC No. : RBRC04200
Strain name : B6;129P2-Cxcr4<tm2Tng>/TngRbrc
RBRC No. : RBRC04198
Related strains : B6;129P2-Cxcr4<tm1Tng>/TngRbrc
Model to human diseases : HIV-1, SUSCEPTIBILITY TO
OMIM ID: 609423
OMIM ID: 193670
References : [1] Ara T, Tokoyoda K, Sugiyama T, Egawa T, Kawabata K, Nagasawa T. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity; 19(2):257-67, 2003.
[2] Kohara H, Omatsu Y, Sugiyama T, Noda M, Fujii N, Nagasawa T. Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling. Blood; 110(13):4153-60, 2007.
[3] Noda M, Omatsu Y, Sugiyama T, Oishi S, Fujii N, Nagasawa T. CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice. Blood; 117(2):451-8, 2011.
[4] Nagasawa T. CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4. J Mol Med.; 92(5):433-9, 2014.
[5] Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity; 20(6):707-18, 2004. 
[6]  Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity; 25(6):977-88, 2006. 
[7] Omatsu Y, 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(3):387-99, 2010. 
[8] Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Nagasawa T, Link DC. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature; 495(7440):227-30, 2013. 
[9] Omatsu Y, Seike M, Sugiyama T, Kume T, Nagasawa T. Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature; 508(7497):536-40, 2014. 


December 2014
Contact: Shinya Ayabe, Ph.D.
Experimental Animal Division, RIKEN BioResource Center
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