Connexin43 is required for the maintenance of multipotency in skin-derived stem cells.
Expression of the gap junction protein, connexin43 (Cx43), begins early during embryogenesis and is maintained in many different cell types. Several stem cell populations have been shown to express Cx43 and to form functional gap junctions. While it is clear that Cx43 is critical to the function of many organs, whether the same is true for stem cells has not been clearly demonstrated. Recently, stem cells isolated from newborn mouse skin were shown to form oocyte-like cells (OLCs) in vitro, hence the present study focussed on the role Cx43 plays in the proliferation and differentiation of these cells. The stem cells express Cx43 and those from knockout mice (Cx43 KO) exhibited significantly reduced cell-cell coupling. Loss of Cx43 reduced the rate of cellular migration [Cx43 KO, 1.57±0.65 radial cell units (RCU); wildtype (WT), 5.57±0.37 RCU] but increased the proliferation rate of the stem cells (Cx43 KO, 29.40%±2.02%; WT, 12.76%±1.50%). The expression of the pluripotency markers OCT4 and Nanog were found to be reduced in the Cx43 KO population, suggesting an inhibition of differentiation potential. To test the differentiation ability, the stem cells were induced to form neuronal cell types in vitro. While both the WT and KO cells were able to form GFAP-positive astrocytic cells, only WT stem cells were able to form βIII tubulin-positive neurons. Similarly, the ability of the stem cells to form OLCs was ablated by the loss of Cx43. These data reveal a role for Cx43 in maintaining multipotency within the skin-derived stem cell population.
1 Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Ontario, Canada .
Paul W
PW
Dyce
Dan
D
Li
Kevin J
KJ
Barr
Gerald M
GM
Kidder
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D017629:Gap Junctions / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D009474:Neurons / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D009865:Oocytes / Q000166:cytology / Q000254:growth & development; D012867:Skin / Q000166:cytology / Q000196:embryology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014404:Tubulin / Q000096:biosynthesis
D018031:Connexin 43; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse