Connexin-43 gap junctions are involved in multiconnexin-expressing stromalsupport of hemopoietic progenitors and stem cells

Gap junctions (GJs) provide for a unique system of intercellular communicat ion (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 b een considered as the predominantly expressed Cx by hematopoietic-supportin g stroma, To investigate the role of the Cx family in hemopoiesis, we analy zed the expression of 11 different Cx species in different stromal cell lin es 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, an d 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 a rea-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 wa s able to restore their diminished IC to the level of the wild-type FL stro mal cells. In addition, these Cx43-reintroduced stromal cells showed an inc reased 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 sug gest that stromal Cx43-mediated IC, although not responsible for all GJ-med iated IC of stromal cells, plays a role In the supportive ability for hemop oietic progenitors and stem cells. (C) 2000 by The American Society of Hema tology.