Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
MetadataShow full item record
Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis.
Showing items related by title, author, creator and subject.
Wells, J.; Howlett, M.; Halse, H.; Heng, J.; Ford, J.; Cheung, Laurence; Samuels, A.; Crook, M.; Charles, A.; Cole, C.; Kees, U. (2016)To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia ...
Kicic, Anthony ; Hall, C.M.; Shen, W.Y.; Rakoczy, P.E. (2005)Autologous stem cell transplantation combined with gene therapy can potentially be used to treat genetically inherited diseases. However, characterization of multipotential cells from a disease state remains extremely ...
Molecular mechanism underlying aberrant expression of the connective tissue growth factor in paediatric pre-B cell acute lymphoblastic leukemiaWelch, Mathew D. (2011)Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children aged 1-14 years. There have been vast improvements in clinical outcomes for children diagnosed with ALL with cure rates of up to 90% ...