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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 498-505
Connexin-43 gap junctions are involved in multiconnexin-expressing
stromal support of hemopoietic progenitors and stem cells
Jose A. Cancelas,
Wendy L. M. Koevoet,
Alexandra
E. de Koning,
Angelique E. M. Mayen,
Elwin J. C. Rombouts, and
Rob E. Ploemacher
From the Department of Hematology, Faculty of Medicine, Erasmus
University of Rotterdam, The Netherlands.
Gap junctions (GJs) provide for a unique system of intercellular
communication (IC) allowing rapid transport of small molecules from
cell to cell. GJs are formed by a large family of proteins named
connexins (Cxs). Cx43 has been considered as the predominantly expressed Cx by hematopoietic-supporting stroma. To investigate the
role of the Cx family in hemopoiesis, we analyzed the expression of 11 different Cx species in different stromal cell lines derived from
murine bone marrow (BM) or fetal liver (FL). We found that up to 5 Cxs
are expressed in FL stromal cells (Cx43, Cx45, Cx30.3, Cx31, and
Cx31.1), whereas only Cx43, Cx45, and Cx31 were clearly detectable in
BM stromal cells. In vivo, the Cx43-deficient 14.5- to 15-day FL
cobblestone area-forming cells (CAFC)-week 1-4 and colony-forming unit
contents were 26%-38% and 39%-47% lower than in their wild-type
counterparts, respectively. The reintroduction of the Cx43 gene into
Cx43-deficient FL stromal cells was able to restore their diminished IC
to the level of the wild-type FL stromal cells. In addition, these
Cx43-reintroduced stromal cells showed an increased support ability
(3.7-fold) for CAFC-week 1 in normal mouse BM and 5-fold higher
supportive ability for CAFC-week 4 in 5-fluorouracil-treated BM cells
as compared with Cx43-deficient FL stromal cells. These findings
suggest that stromal Cx43-mediated IC, although not responsible for all
GJ-mediated IC of stromal cells, plays a role in the supportive ability
for hemopoietic progenitors and stem cells.
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