In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study.

BACKGROUND

Exposure to intrauterine obesity can disrupt clock gene rhythmicity in animal models. The aim of this pilot study was to determine if maternal obesity alters rhythmic expression of core clock in mesenchymal stem cells (MSCs) from umbilical cords of human infants born to mothers with obesity (Ob-MSC) vs. normal weight (NW-MSC).

METHODS

We compared in vitro rhythmic expression patterns of core clock (, , ) and clock-output (), components in undifferentiated Ob-MSCs ( = 3) vs. NW-MSCs ( = 3). MSCs were harvested every 2 h, following a dexamethasone shock, for 30 h. Adipogenesis or myogenesis was induced in vitro and markers of adipogenesis and fat storage were assessed, respectively.

RESULTS

We detected significant rhythmicity in expression patterns of , , and at the group level in Ob- and NW-MSCs ( < 0.05). PER2 oscillatory amplitude was 3-fold higher in Ob-MSCs vs. NW-MSCs ( < 0.006). During adipogenesis, Ob-MSCs had higher PPAR protein content ( = 0.04) vs. NW-MSC. During myogenesis, Ob-MSCs had higher saturated triacylglycerols ( = 0.04) vs. NW-MSC.

CONCLUSION

Rhythmic expressions of , , and are detectable in undifferentiated MSCs. Higher oscillatory amplitude was paralleled by higher markers of fat storage during differentiation in Ob-MSCs vs. NW-MSCs, and supports that the core clock and cellular metabolism may be linked in infant MSCs.