Circadian Gene BMAL1 Regulation of Cell Senescence in Thyroid aging [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA1150075 | ENA |
REPOSITORIES: ENA
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Project description:As the global aging society intensifies, the incidence of thyroid diseases among the elderly is increasing annually, with hypothyroidism being particularly common. Studies have shown that in healthy elderly individuals, thyroid-stimulating hormone (TSH) levels are significantly elevated, while thyroid hormone (TH) levels are notably normal or decreased. However, the molecular mechanisms underlying thyroid aging and function remain unclear. To understand thyroid aging, it is essential to study the molecular and functional characteristics of various thyroid cell types during the aging process. We conducted single-cell sequencing of thyroids from different age groups and identified eight typical cell types and five thyroid epithelial cell subtypes (EPI). During aging, the expression levels of thyroid hormone synthesis-related genes (TSHR, TG, TPO) increased, suggesting that EPI cells adjust their gene expression patterns in response to elevated TSH. With advancing age, rhythmic disruption and cellular senescence signals accumulated in thyroid. Further analysis indicated that the senescent EPI cell subpopulation (CDKN1A_EPI) exhibited functional decline. Additionally, we unexpectedly found that the expression of the core circadian gene BMAL1 (ARNTL) was downregulated in the CDKN1A_EPI cells of elderly individuals. To verify this finding, we used a thyroid-specific knockout mouse model and found that BMAL1 downregulation inhibited NFKBIA expression, exacerbating cellular senescence. Finally, cell line knockout experiments and transcriptome sequencing further confirmed that BMAL1 knockout led to decreased expression of NF-kB Inhibitor Alpha (NFKBIA), a key mechanism driving thyroid cell senescence. This discovery not only reveals the relationship between thyroid cell aging and circadian rhythm disruption but also enriches our understanding of the mechanisms underlying thyroid aging.
2025-08-01 | GSE275234 | GEO
Project description:As the global aging society intensifies, the incidence of thyroid diseases among the elderly is increasing annually, with hypothyroidism being particularly common. Studies have shown that in healthy elderly individuals, thyroid-stimulating hormone (TSH) levels are significantly elevated, while thyroid hormone (TH) levels are notably normal or decreased. However, the molecular mechanisms underlying thyroid aging and function remain unclear. To understand thyroid aging, it is essential to study the molecular and functional characteristics of various thyroid cell types during the aging process. We conducted single-cell sequencing of thyroids from different age groups and identified eight typical cell types and five thyroid epithelial cell subtypes (EPI). During aging, the expression levels of thyroid hormone synthesis-related genes (TSHR, TG, TPO) increased, suggesting that EPI cells adjust their gene expression patterns in response to elevated TSH. With advancing age, rhythmic disruption and cellular senescence signals accumulated in thyroid. Further analysis indicated that the senescent EPI cell subpopulation (CDKN1A_EPI) exhibited functional decline. Additionally, we unexpectedly found that the expression of the core circadian gene BMAL1 (ARNTL) was downregulated in the CDKN1A_EPI cells of elderly individuals. To verify this finding, we used a thyroid-specific knockout mouse model and found that BMAL1 downregulation inhibited NFKBIA expression, exacerbating cellular senescence. Finally, cell line knockout experiments and transcriptome sequencing further confirmed that BMAL1 knockout led to decreased expression of NF-kB Inhibitor Alpha (NFKBIA), a key mechanism driving thyroid cell senescence. This discovery not only reveals the relationship between thyroid cell aging and circadian rhythm disruption but also enriches our understanding of the mechanisms underlying thyroid aging.
2025-08-01 | GSE275233 | GEO
Project description:Circadian Gene BMAL1 Regulation of Cell Senescence in Thyroid aging [scRNA-Seq]
| PRJNA1150072 | ENA
Project description:Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are interdependent has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. In this study, we show that BMAL1 in is uniquely localized to genomic motifs associated with AP-1 in senescent cells and contributes to AP-1 transcriptional control of the senescence program.
2023-08-22 | GSE229009 | GEO
Project description:Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are interdependent has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. In this study, we show that BMAL1 in is uniquely localized to genomic motifs associated with AP-1 in senescent cells and contributes to AP-1 transcriptional control of the senescence program.
2023-08-22 | GSE229011 | GEO
Project description:Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are interdependent has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. In this study, we show that BMAL1 in is uniquely localized to genomic motifs associated with AP-1 in senescent cells and contributes to AP-1 transcriptional control of the senescence program.
2023-08-22 | GSE229010 | GEO
Project description:Here we reveal a novel role for the circadian clock gene Bmal1 and Period2 in regulating the spatial organization of the cone opsins. Deletion of Bmal1 and Per2 have opposing effects on S-opsin expression and patterning of the cone photoreceptors is disrupted in cone specific knockouts of these genes. Using ChIP analysis we show that BMAL1 directly binds to the promoter region of the thyroid activating enzyme type II deiodinase (Dio2).
2017-10-17 | GSE103484 | GEO
Project description:Advances in circadian research revealed an intricate relationship between aging and circadian rhythms. However, whether and how the circadian machinery contribute to stem cell aging, especially in primates, remains poorly understood. In this study, we investigated the role of BMAL1, the only non-redundant circadian clock component, during aging in mesenchymal progenitor cells (MPCs). We observed an accelerated aging phenotype in both BMAL1 deficient human and cynomolgus monkey MPCs. Notably, this phenotype is mainly attributed to a transcriptional-independent role of BMAL1 in stabilizing the heterochromatin and thus preventing LINE1 activation. In senescent MPCs from human and cynomolgus monkeys, dampened LINE1 binding capacity of BMAL1 and synergistically activated LINE1 transcripts were observed. Furthermore, similar de-stabilized heterochromatin and aberrant LINE1s transcription was observed in the skin and muscle tissues from BMAL1-deficient cynomolgus monkey. Altogether, these findings uncover a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primates.
2022-03-18 | PXD030570 | Pride
Project description:Cardiac injury following myocardial infarction exhibits a circadian pattern, yet the underlying mechanism remains unclear. To elucidate genes governing circadian variation of myocardial injury, we conducted transcriptomic profiling of left-ventricular tissues from mice or humans experiencing myocardial injury at different daytimes. Through comprehensive analyses, including transgenic mouse models and functional studies, we identified BMAL1 as a pivotal transcription factor modulating diurnal variation of myocardial injury. Remarkably, we discovered that BMAL1 regulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with HIF2A. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2F/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1. Furthermore, we confirmed amphiregulin (AREG) as a transcriptional target of the BMAL1/HIF2A heterodimer, critical for modulating circadian variation of myocardial injury. Finally, targeting the BMAL1/HIF2A-AREG pathway via timed AREG administration or enhancing circadian rhythm pharmacologically offered significant cardioprotection, implicating this pathway in treating ischemic heart disease.
2024-03-20 | GSE255307 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38622: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [telogen]. GSE38623: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [Anagen] GSE38624: Bmal1 controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis [Bmal1 KO] Refer to individual Series
2012-08-01 | E-GEOD-38625 | biostudies-arrayexpress