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 obes...
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MDPI AG
2023-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/16/1/52 |
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| author | Melissa L. Erickson Devin Dobias Madeline Rose Keleher Dana Dabelea Bryan C. Bergman Josiane L. Broussard Kristen E. Boyle |
| author_facet | Melissa L. Erickson Devin Dobias Madeline Rose Keleher Dana Dabelea Bryan C. Bergman Josiane L. Broussard Kristen E. Boyle |
| author_sort | Melissa L. Erickson |
| collection | DOAJ |
| description | 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 (<i>BMAL1</i>, <i>CLOCK</i>, <i>PER2</i>) and clock-output (<i>NR1D1</i>), components in undifferentiated Ob-MSCs (<i>n</i> = 3) vs. NW-MSCs (<i>n</i> = 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 <i>BMAL1</i>, <i>PER2</i>, and <i>NR1D1</i> at the group level in Ob- and NW-MSCs (<i>p</i> < 0.05). PER2 oscillatory amplitude was 3-fold higher in Ob-MSCs vs. NW-MSCs (<i>p</i> < 0.006). During adipogenesis, Ob-MSCs had higher PPAR<i>γ</i> protein content (<i>p</i> = 0.04) vs. NW-MSC. During myogenesis, Ob-MSCs had higher saturated triacylglycerols (<i>p</i> = 0.04) vs. NW-MSC. Conclusion: Rhythmic expressions of <i>BMAL1</i>, <i>PER2</i>, and <i>NR1D1</i> are detectable in undifferentiated MSCs. Higher <i>PER2</i> 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. |
| first_indexed | 2024-03-08T15:00:04Z |
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| id | doaj.art-1f88dc2175c8499ca0a228a751bf70ed |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-08T15:00:04Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-1f88dc2175c8499ca0a228a751bf70ed2024-01-10T15:05:22ZengMDPI AGNutrients2072-66432023-12-011615210.3390/nu16010052In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot StudyMelissa L. Erickson0Devin Dobias1Madeline Rose Keleher2Dana Dabelea3Bryan C. Bergman4Josiane L. Broussard5Kristen E. Boyle6Translational Research Institute, AdventHealth, Orlando, FL 32804, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USAThe Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, CO 80045, USADivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USABackground: 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 (<i>BMAL1</i>, <i>CLOCK</i>, <i>PER2</i>) and clock-output (<i>NR1D1</i>), components in undifferentiated Ob-MSCs (<i>n</i> = 3) vs. NW-MSCs (<i>n</i> = 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 <i>BMAL1</i>, <i>PER2</i>, and <i>NR1D1</i> at the group level in Ob- and NW-MSCs (<i>p</i> < 0.05). PER2 oscillatory amplitude was 3-fold higher in Ob-MSCs vs. NW-MSCs (<i>p</i> < 0.006). During adipogenesis, Ob-MSCs had higher PPAR<i>γ</i> protein content (<i>p</i> = 0.04) vs. NW-MSC. During myogenesis, Ob-MSCs had higher saturated triacylglycerols (<i>p</i> = 0.04) vs. NW-MSC. Conclusion: Rhythmic expressions of <i>BMAL1</i>, <i>PER2</i>, and <i>NR1D1</i> are detectable in undifferentiated MSCs. Higher <i>PER2</i> 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.https://www.mdpi.com/2072-6643/16/1/52circadianobesitymaternalmesenchymal stem cells |
| spellingShingle | Melissa L. Erickson Devin Dobias Madeline Rose Keleher Dana Dabelea Bryan C. Bergman Josiane L. Broussard Kristen E. Boyle In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study Nutrients circadian obesity maternal mesenchymal stem cells |
| title | In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study |
| title_full | In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study |
| title_fullStr | In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study |
| title_full_unstemmed | In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study |
| title_short | In Vitro Circadian Clock Gene Expression Assessments in Mesenchymal Stem Cells from Human Infants: A Pilot Study |
| title_sort | in vitro circadian clock gene expression assessments in mesenchymal stem cells from human infants a pilot study |
| topic | circadian obesity maternal mesenchymal stem cells |
| url | https://www.mdpi.com/2072-6643/16/1/52 |
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