Detecting Circadian Rhythmicity By Single Cell Multiomics
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE288579 | GEO | 2026/02/04
REPOSITORIES: GEO
Similar Datasets
Project description:Detecting Circadian Rhythmicity By Single Cell Multiomics
| PRJNA1218624 | ENA
Project description:Fibroblasts can be reprogrammed to induced neurons (iNs) via transducion of Ascl1, Brn2, and Myt1l. To understand the roles of the circadian regulators Per1 and Per2 on the reprogramming, embryonic fibroblasts from wild type (WT), Per1-/-, and Per2-/- mice were transduced with the three genes and cells were harvested for scRNA-seq on days 4, 7, and 10 after transduction.
2023-11-09 | GSE227621 | GEO
Project description:Disruption of circadian rhythms predisposes shift workers to many chronic conditions, including osteoporosis. However, the effects of disrupted circadian rhythms on bone remodeling remain largely unknown. Here, we show that one of the core circadian regulators PER1 inhibits osteoclastogenesis by upregulating genes involved in inflammation. The conditional knockout of Per1 in osteoclasts and related cells resulted in decreased bone mass in the femurs of mice, along with increased osteoclasts and decreased osteoblasts. Osteoclastogenesis was also promoted by Per1 depletion in vitro with 16 downregulated inflammatory genes. Seven of these genes were known to promote or inhibit osteoclastogenesis depending on the stage of osteoclastogenesis and the presence or absence of infection. Knockdown of Nlrp3, Tlr8, or Tlr9 in the group of genes promoted osteoclastogenesis, mirroring the effects of Per1 knockout and offering a mechanistic explanation for the Per1-mediated inhibition of osteoclastogenesis. These results were not observed following the knockout of a paralog Per2. Per1 knockout mice maintain general circadian rhythms, unlike arrhythmic Per1;Per2 double knockout mice. This gives credence to Per1 as a selective target for therapeutic interventions without disrupting the circadian rhythms. This study uncovered a molecular link between a circadian regulator and osteoclastogenesis in the broader context of inflammatory reactions. Our findings may be mechanistically relevant to inflammatory bone diseases influenced by circadian rhythms, such as rheumatoid arthritis and osteoarthritis, as well as other bone diseases predisposed by chronic circadian disruption.
2026-02-12 | GSE283894 | GEO
Project description:Disruption of circadian rhythms predisposes shift workers to many chronic conditions, including osteoporosis. However, the effects of disrupted circadian rhythms on bone remodeling remain largely unknown. Here, we show that one of the core circadian regulators PER1 inhibits osteoclastogenesis by upregulating genes involved in inflammation. The conditional knockout of Per1 in osteoclasts and related cells resulted in decreased bone mass in the femurs of mice, along with increased osteoclasts and decreased osteoblasts. Osteoclastogenesis was also promoted by Per1 depletion in vitro with 16 downregulated inflammatory genes. Seven of these genes were known to promote or inhibit osteoclastogenesis depending on the stage of osteoclastogenesis and the presence or absence of infection. Knockdown of Nlrp3, Tlr8, or Tlr9 in the group of genes promoted osteoclastogenesis, mirroring the effects of Per1 knockout and offering a mechanistic explanation for the Per1-mediated inhibition of osteoclastogenesis. These results were not observed following the knockout of a paralog Per2. Per1 knockout mice maintain general circadian rhythms, unlike arrhythmic Per1;Per2 double knockout mice. This gives credence to Per1 as a selective target for therapeutic interventions without disrupting the circadian rhythms. This study uncovered a molecular link between a circadian regulator and osteoclastogenesis in the broader context of inflammatory reactions. Our findings may be mechanistically relevant to inflammatory bone diseases influenced by circadian rhythms, such as rheumatoid arthritis and osteoarthritis, as well as other bone diseases predisposed by chronic circadian disruption.
2026-02-12 | GSE292534 | GEO
Project description:Circadian rhythms regulate cell differentiation and tissue regeneration; however, their implications in tissue regeneration remain elusive. Here, we present evidence that tissue regeneration efficiency is dependent on the circadian timing of injury affliction in a mouse model of muscle injury. We found that depletion of Per1 or Per2, members of the core circadian regulators in vertebrates, impaired mouse muscle regeneration and myoblast differentiation. Both Per1 and Per2 were necessary to maintain the expression level of Igf2, one of the critical regulators for myoblast differentiation, through epigenetic regulation at the Igf2 promoter and enhancer. Reflecting this, myoblast differentiation was promoted when differentiation was initiated while the level of Pers and Igf2 were high, compared with the time when their expression levels were low. Furthermore, muscle regeneration in the mouse was more efficient when chemical injury was inflicted at night when Pers were highly expressed, compared with morning injury. This study uncovers circadian timing-based control of myoblast differentiation and muscle regeneration.
2021-04-27 | GSE150785 | GEO
Project description:a circadian proteome atlas of eight organs, namely suprachiasmatic nucleus (SCN), hypothalamus (HPOA), liver (LIV), gall bladder (GBD), brown adipose tissue (BAT), kidney (KDN), heart (HEA) and muscle (MUS), from wild-type (WT) and Per1-/-/Per2-/- (DKO) mice housed under constant darkness and ad libitum feeding, collected every two hours for deep proteomic analysis over two days
2023-11-28 | PXD047352 |
Project description:Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor Outer Segment (POS) phagocytosis occurs as a daily peak, roughly about one hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2), lack a daily peak in POS phagocytosis. By qPCR analysis we found that core clock genes were rhythmic over 24h in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time-points preceding and during the peak of POS phagocytosis. By contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time-point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time-point. Finally, based on STRING analysis we found a group of interacting genes which potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE.
2021-06-01 | GSE172437 | GEO
Project description:Retinal photoreceptors undergo daily renewal of their distal outer segments, a process indispensable for maintaining retinal health. Photoreceptor Outer Segment (POS) phagocytosis occurs as a daily peak, roughly about one hour after light onset. However, the underlying cellular and molecular mechanisms which initiate this process are still unknown. Here we show that, under constant darkness, mice deficient for core circadian clock genes (Per1 and Per2), lack a daily peak in POS phagocytosis. By qPCR analysis we found that core clock genes were rhythmic over 24h in both WT and Per1, Per2 double mutant whole retinas. More precise transcriptomics analysis of laser capture microdissected WT photoreceptors revealed no differentially expressed genes between time-points preceding and during the peak of POS phagocytosis. By contrast, we found that microdissected WT retinal pigment epithelium (RPE) had a number of genes that were differentially expressed at the peak phagocytic time-point compared to adjacent ones. We also found a number of differentially expressed genes in Per1, Per2 double mutant RPE compared to WT ones at the peak phagocytic time-point. Finally, based on STRING analysis we found a group of interacting genes which potentially drive POS phagocytosis in the RPE. This potential pathway consists of genes such as: Pacsin1, Syp, Camk2b and Camk2d among others. Our findings indicate that Per1 and Per2 are necessary clock components for driving POS phagocytosis and suggest that this process is transcriptionally driven by the RPE.
2021-06-01 | GSE172438 | GEO
Project description:Circadian rhythms in gene expression are coincident with 24hr dynamics in the recruitment of the core-clock transcription factor heterodimer CLOCK-BMAL1 to chromatin. In the liver, circadian chromatin is characterized by rhythmic histone modifications and the deposition of histone variant H2A.Z. However, other histone variants and the remodelers that work in conjunction with CLOCK-BMAL1 on variant chromatin remain poorly understood. Here, we reveal that H3.3 variant histone deposition peaks during the daytime in liver chromatin and that CLOCK-BMAL1 is recruited to H3.3 nucleosomes. Moreover, H3.3:CLOCK-BMAL1 associates with PBAF and BRG1/cBAF complexes - members of the SWI/SNF remodeler family - only during the active phase of the circadian cycle. In clock-disrupted Per1-/-; Per2-/- livers, we observe a depletion in ARID2, the central cog in the molecular assembly of the PBAF complex, accompanied by an increase in H3.3 incorporation. Remarkably, a disassembly of PBAF complex and the concurrent reduction in BRG1 triggers a remodeler reorganization in Per knockout livers, where BRM/cBAF now targets BMAL1 at readily-accessible genomic sites. An abundance of fragile acetylated H3.3 nucleosomes and a remodeler reorganization provide a mechanistic basis for BMAL1 activity in the absence of PER-mediated negative feedback.
2025-08-22 | PXD061974 | Pride
Project description:The circadian clock regulates diverse physiological processes by maintaining a 24-hour gene expression pattern. Genetic and environmental cues that disrupt normal clock rhythms can lead to cancer, yet the extent to which this effect is controlled by the cancer cells versus non-malignant cells in the tumor microenvironment (TME) is not clear. Here we set out to address this question, by selective manipulation of circadian clock genes in the TME. In two different mouse models of cancer we find that expression of the core clock gene Per2 in the TME is crucial for tumor initiation and metastatic colonization, whereas another core gene, Per1, is dispensable. We further show that loss of Per2 in the TME leads to significant transcriptional changes in response to cancer cell introduction. These changes may contribute to a tumor-suppressive microenvironment. Thus, our work unravels an unexpected protumorigenic role for the core clock gene Per2 in the TME, with potential implications for therapeutic dosing strategies and treatment regimens.
2020-10-15 | GSE156450 | GEO