Suppression of hematopoietic activity in tenascin-C-deficient mice.
Tenascin-C (TN-C), a member of the extracellular matrix (ECM) glycoprotein family, is expressed on the surface of stromal cells in the hematopoietic system or lymphoid organs. Recently, TN-C-deficient mutant mice produced by TN-C gene targeting through homologous recombination were shown to develop normally, although TNs have been reported to play important roles in organogenesis and carcinogenesis. In the present study, we found that colony-forming capacity of bone marrow (BM) cells was considerably lower in TN-C-deficient mice (a decrease of approximately 35% from control), although their mononuclear cell count and BM architecture showed no significant difference from those of normal mice. Furthermore, in long-term BM culture in vitro, hematopoietic cell production (a decrease of approximately 40% in Dexter's condition and of approximately 65% in Whitlock-Witte's condition from control), colony-forming capacity of the produced cells (a decrease of approximately 60% from control), and longevity of the cultures were markedly lower in the TN-C-deficient mice than in control mice, whereas hematopoiesis in the TN-C-deficient mutant mice was sustained. The addition of TN-C glycoprotein to long-term BM cultures of TN-C-deficient mice clearly induced the recovery of hematopoietic cell production and colony-forming capacity of hematopoietic progenitor cells. Thus, these results provide direct evidence that an ECM glycoprotein component, TN-C, plays a relevant role in hematopoiesis through interactions between stromal cells and hematopoietic progenitor cells.
Ohta
M
M
Division of Biochemistry, Cancer Institute, Hokkaido University, School of Medicine, Sapporo, Japan.
Sakai
T
T
Saga
Y
Y
Aizawa
S
S
Saito
M
M
D000818:Animals; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D019084:Fluorescent Antibody Technique, Indirect; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017154:Stromal Cells / Q000166:cytology; D019063:Tenascin / Q000172:deficiency*
D019063:Tenascin