Table 1.
Connexin expression and GJIC in ES cells.
| ES cell lines | Connexin expression in undifferentiated cells | GJIC in undifferentiated cells | Differentiation from ES cells | Connexin expression during differentiation | GJIC during differentiation | Methods used to determine the final phenotype of differentiated cells | References |
|---|---|---|---|---|---|---|---|
| Mouse ES cells (J1) | Cx431, Cx451 Not detected: Cx401 | Present3 | Cardiomyocytes | Cx401, Cx431, 2, Cx451 | Present3. Restricted to neighboring beating cells | Contraction, Ca2+-imaging, cardiac-specific gene expression | Oyamada et al., 1996 |
| Mouse ES cells (D3) | Cardiomyocytes | Cx432 | Present3 | Contraction, EM | Westfall et al., 1997 | ||
| Mouse Cx43−/− ES cells (R1) | Cx451. No compensatory upregulation of Cx401 and Cx451 | Very low GJIC3 | Cardiomyocytes. Cx43 knockout did not significantly change either the time course, frequency of cardiomyocytic differentiation, or expression of cardiac-specific genes | Upregulation of Cx401 | Very low GJIC3 | Contraction, cardiac-specific gene expression | Oyamada et al., 2000 |
| Mouse ES cells (D3) | Cx431, 2 | Cardiomyocytes | Increases in Cx402 and Cx432 during cardiac differentiation | Contraction, cardiac-specific gene expression, electrophysiology | Van Kempen et al., 2003 | ||
| Mouse ES cells (HM1) | Cardiomyocytes | Upregulation of Cx402 at a peak around day 3 (hanging drop period) + 14 | Cardiac-specific gene expression, ANEPPS fluorescence, electrophysiology | Fijnvandraat et al., 2003 | |||
| Mouse ES cells (CCE) | Cx431, 2, Cx451, 2 No or very low expression: Cx371, Cx401 | Cardiomyocytes (irregular contractions in Cx45−/− cells) | Cx371, Cx401, Cx431, 2, Cx451 | Contraction, Ca2+-imaging, multielectrode array, cardiac-specific gene expression, EM | Egashira et al., 2004 | ||
| Human ES cells (H1, H7, H9, H14) | Cx431, 2, Cx451 | Present3 | Carpenter et al., 2004 | ||||
| Human ES cells (GE01, GE09, BG01, BG02, TE06) | Cx431, Cx451 | Bhattacharya et al., 2004 | |||||
| Human ES cells (HES-3, HES-4) | Cx431 (As one of the candidate human ES marker genes) | Richards et al., 2004 | |||||
| Human ES cells (HES-3, HES-4) | Cx431, 2, Cx451, 2 | Present3 | Wong et al., 2004, 2006 | ||||
| Mouse ES cells (Royan B1) | Cardiomyocytes | Presence of gap junctions in 21-day cardiomyocytes by EM | Cardiac-specific gene expression, EM, pharmacological reagents | Baharvand et al., 2005 | |||
| Mouse ES cells (DBA/1LacJ) | Cardiomyocytes | Cx431, Cx451 | Contraction, Ca2+-imaging, cardiac-specific gene expression, EM | Chaudhary et al., 2006 | |||
| Human ES cells (BG01, H1) | Cx431, 2, Cx401, 2, Cx451, 2, Cx251, Cx261, Cx301, Cx30.21, Cx30.31, Cx311, Cx31.11, Cx31.91, Cx321, Cx361, Cx371, Cx461, Cx471, Cx591, Cx621 Not detected: Cx40.11, Cx501 | Presence of GJIC3, 5 and hemichannels Extremely rare dye coupling between ES cells and feeder cells | Contraction, electrophysiology, cardiac-specific gene expression, EM, pharmacological reagents | Huettner et al., 2006 | |||
| Cynomolgus monkey ES cells (CMK-6) | Cx431 | Embryoid bodies (EBs) | Suppression of Cx43 mRNA expression during EB differentiation | Yamamoto et al., 2007 | |||
| Human ES cells (HES2, HES-3, ENVY) | Cx432 | Presence of GJIC mediated transport of shRNA | Wolvetang et al., 2007 | ||||
| Mouse ES cells (D3) | Cx431, 2 | Present3. Cx43 silencing inhibited GJIC, induced a loss of pluripotent state, and decreased in the proliferation rate | EBs GJIC blockers and Cx43-siRNA inhibited the formation of EBs from ES cells | Todorova et al., 2008 | |||
| Mouse ES cells (HM1) | Cx431, 2, Cx451, 2, Cx311, 2, Cx261, Cx30.31, Cx321, Cx371 Not detected: Cx262, Cx291, Cx301, Cx30.21, Cx31.11, Cx322, Cx331, Cx361, Cx372, Cx401, Cx461, Cx471, Cx501, Cx571 | Present3, 4 Reduction of GJIC by decreased expression of Cx31 or Cx45 via RNA interference in Cx43−/− ES cells did not lead to apoptosis | Worsdorfer et al., 2008 | ||||
| Mouse ES cells (D3): Sox1-promoter-GFP + ES cells and Cx43−/− ES cells | Cx431 | Neuroectodermal cells Cx43−/− ES cells showed a failure of oligodendrocyte development and an amplification of astrocytic cells | Wild-type ES cells showed “two-tailed” Cx43 expression with a maximum at day 7 | Sox1-promoter-GFP, neuronal lineage-specific gene expression | Parekkadan et al., 2008 | ||
| Human ES cells (hESM01) | Present3 | Not characterized | Present but attenuated3 Restricted to differentiated cells Absence of GJIC between pluripotent and differentiating cells | Sharovskaya et al., 2009 | |||
| Mouse ES cells (R1) | Cardiomyocytes | Cx432 expression in cell sheets of mouse ES cell-derived cardiomyocytes | Cardiac-specific gene expression, multielectrode array | Matsuura et al., 2011 |
1
mRNA level;
2
Protein level;
3
dye coupling (Lucifer yellow etc.);
4
neurobiotin tracer coupling;
5
electrical coupling; EM, electron microscopy.