| Gene name: | GATA6 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | iPSC-MSC |
| Experiment: | SA-β-gal activity assay//qRT-PCR |
| Description: | GATA6 knockdown in cells at the late passage significantly reduced the ratio of senescent to total cells whereas that in cells at the early passage did not. Similarly, GATA6 knockdown markedly decreased the expression of p53 and p21CIP1 and significantly increased the expression of CDK1 in late-passage cells but did not affect early-passage cells. Other than the effect on cell cycle regulators, GATA6 knockdown significantly downregulated mRNA levels of senescence-associated secretory phenotype (SASP) marker IL6 and IL1B in late-passage as well as early-passage iPSC-MSCs. |
| Regulatory pathway: | SHH-FOXP1 |
| R-AG-Pathway: | Downregulation |
| Pathway experiment: | SA-β-gal activity assay//Western blot |
| Pathway description: | Knockdown of GATA6 resulted in an increase in the expression of the SHH signaling molecule SHH, SMO, and GLI1 as well as FOXP1, suggesting that GATA6 is an upstream inhibitory regulator of both SHH signaling and FOXP1. When the expression of SMO, a key molecule in the SHH pathway, was repressed, the expression of its downstream molecule GLI1 was decreased as well as that of FOXP1. There was a significantly lower ratio of cells stained positive for SA-β-gal in the culture of GATA6-knockdown cells compared to that in the culture of control cells whereas the opposite trend was shown between the culture of FOXP1-knockdown and control cells, suggesting that repressing the expression of GATA6 or FOXP1 leads to attenuation or increase of cellular senescence, respectively. Results of DNA content analysis showed that repressing the expression of GATA6 in iPSC-MSCs promoted cell proliferation whereas that of FOXP1 significantly inhibited cell proliferation. In terms of the activity of senescence- and cell cycle-associated markers, GATA6 knockdown resulted in a significant decrease in the expression of p53 and p21CIP1 and a significant increase in the expression of CDK1. Conversely, FOXP1 knockdown significantly increased the p53 and p21CIP1 expression and significantly decreased the CDK1 expression. |
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