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Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice
Masatsugu Ohta,
Takao Sakai,
Yumiko Saga,
Shin-ichi Aizawa, and
Masaki Saito
From the Division of Biochemistry, Cancer Institute, Hokkaido
University, School of Medicine, Sapporo; the Division of Hemopoiesis,
Institute of Hematology, Department of Medicine, Jichi Medical School,
Tochigi; Cellular and Molecular Toxicology Division, National Institute
of Health Sciences, Tokyo; Laboratory of Morphogenesis, Institute of
Molecular Embryology and Genetics, Kumamoto University, School of
Medicine, Kumamoto, Japan; and the Departments of Medicine
and Biomolecular Chemistry, University of Wisconsin-Madison,
Madison, WI.
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 ~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 ~40% in Dexter's
condition and of ~65% in Whitlock-Witte's condition from control),
colony-forming capacity of the produced cells (a decrease of ~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.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4074-4083
© 1998 by The American Society of Hematology.
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