Effects of SIK3 KO on the transcriptome in CA1 region
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278753 | GEO | 2026/06/11
REPOSITORIES: GEO
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Project description:Effects of SIK3 KO on the transcriptome in CA1 region
| PRJNA1168572 | ENA
Project description:Osteoarthritis is a common joint disorder that causes debilitating conditions among the elderly. Risk factors of osteoarthritis include age, which is often associated with the thinning of articular cartilage. We generated conditional knockout mice that lack salt-inducible kinase 3 (Sik3) specifically in chondrocytes after birth by tamoxifen administration. Deletion of Sik3 at 2 or 8 weeks after birth increased the thickness of articular cartilage by increasing the chondrocyte population. Additionally, Sik3 deletion protected cartilage against osteoarthritis development. We identified the edible Pteridium aquilinum ingredient, pterosin B, as a compound that inhibits the Sik3 pathway. Intraarticular injection of pterosin B protected cartilage against osteoarthritis development. Sik3 deletion or pterosin B treatment inhibited activation of the hypertrophic program through the histone deacetylase 4 (Hdac4) pathway, increased Prg4 expression in chondrocytes, and protected cartilage against osteoarthritic attack. Collectively, our results suggest Sik3 is a regulator that regulates homeostasis of articular cartilage thickness and a target for treatment of osteoarthritis, and that pterosin B can be the lead compound for relevant drugs.
2016-03-21 | GSE75995 | GEO
Project description:Maintenance of bone homeostasis and the balance between bone resorption and formation are crucial for maintaining skeletal integrity. Osteoclasts are responsible for bone resorption and play a vital role in this process. The role of salt-inducible kinase 3 (SIK3) in osteoclast differentiation and maturation and its potential as a therapeutic target for osteoporosis remain poorly understood. Here, we generated osteoclast-specific Sik3 conditional knockout (cKO) mice and investigated the effects of SIK3 deletion on bone homeostasis. Our findings revealed increased bone mineral density and an osteopetrosis phenotype in Sik3 cKO mice, indicating the involvement of SIK3 in bone resorption. Furthermore, we examined the effect of pterosin B, an SIK3 inhibitor, on osteoclast differentiation. Pterosin B treatment inhibits osteoclast differentiation in vitro, reduces the number of multinucleated osteoclasts, and suppresses bone resorption. Therefore, in this study, to better understand the molecular mechanism of SIK3 in osteoclast differentiation and maturation, we performed gene expression profiling of bone marrow monocytes from SIK3 deletion and pterosin B treated mice using RNA sequencing (RNA-seq).
2024-07-21 | GSE234221 | GEO
Project description:Sleep supports a variety of physiological processes, ranging from metabolic to immune system homeostasis, and plays a critical role in cognition and memory. A brief period of sleep loss impairs memory, particularly hippocampus-dependent memories, and alters molecular signaling and synaptic plasticity in the hippocampus. Studies have shown that sleep deprivation (SD), alters neuronal activation as indicated by broad changes in gene expression signatures and by the altered expression of c-Fos, an immediate early gene (IEG) that functions as a molecular marker of neuronal activity. In the present study, we examined hippocampal subregion-specific c-Fos induction patterns via immunohistochemical staining. We find that CA1 pyramidal neurons exhibit the most robust c-Fos induction after SD. Using an activity-driven ribosomal tagging system and a repeated SD model, we labeled sleep deprivation activated CA1 neurons and identified a specific population of excitatory neurons in area CA1 that are reactivated by repeated SD. Based on the c-Fos-RiboTag system, we performed fosTRAP-seq and identified activity-dependent gene expression changes in c-Fos+ CA1 neurons. Our results revealed that synapse organization, protein dephosphorylation, cellular response to endogenous stimulus (such as insulin) being upregulated, whereas mRNA processing and splicing being downregulated. In summary, our study provides a detailed view of the activation of hippocampal neurons after SD, revealing a subset of CA1 pyramidal neurons having higher sensitivity to the effect of sleep loss, shown as reactivation during repeated SD, allows investigation of molecular changes in neurons specifically impacted by repeated sleep loss. Our work uncovers a population of CA1 pyramidal neurons that are sensitive to repeated sleep loss and sheds light on a possible connection between acute and chronic sleep loss at the cellular and molecular levels.
2026-05-20 | GSE316227 | GEO
Project description:Repeated sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons
| PRJNA1401827 | ENA
Project description:We aimed at investigating the function of TIP60 in the in the mammalian hippocampus. For this, we used mice with a forebrain-specific deletion of Tip60 upon tamoxifen injection (Tip60 cKO). RNA-sequencing was applied to examine the transcriptome changes in the CA1 region upon Tip60 deletion. We observed massive transcriptional changes and identified a neurodegeneration-related signature at a time when there are no obvious morphological changes in Tip60 cKO mice. Later on these mice develop extensive neurodegeneration in hippocampal CA1.
2019-10-24 | GSE139298 | GEO
Project description:Purpose：To identify piRNAs bound to Piwil2 in Sham,transient Global Cerebral Ischemia(tGCI) and transient Global Cerebral Ischemia(tGCI) with Hypoxic Postconditioning (HPC). Methods: Samples from CA1 subregion were lysed in 500 μl lysis buffer and centrifuged. After centrifugation, supernatant was incubated with monoclonal mouse antibody against Piwil2 (Santa Cruz, California, CA, USA), preincubated with Protein A/G Agarose. The beads were washed twice with lysis buffer. After quality check by Western blot, the RNA was extracted from the magnetic beads using Trizol reagent (Invitrogen). Then, the immunoprecipitated RNA was analyzed with piRNAs sequencing. Results: After tGCI, a total of 423 piRNAs interacted with Piwil2 in CA1 was upregulated after 26 h of reperfusion. Of the 423 piRNAs, 317 were significantly upregulated by more than 1.5-fold. Of the 317 piRNAs, 258 showed ≥2-fold change. Comparison between tGCI and HPC groups revealed that 401 piRNAs interacted with Piwil2 in CA1 were significantly downregulated after HPC, whereas only 7 piRNAs were found to be altered in all 3 groups studied (≥1.5-fold change). Conclusions: In our study, we identified a cohort of piRNAs in CA1 of rats. We demonstrated directly contrast changes of piRNAs interacted with Piwil2 in CA1 after tGCI, as compared to those in HPC rats. The results of the prediction showed that DNMT3A may be a potential common target of the 7 differentially expressed piRNAs interacted with Piwil2. Therefore, we focused on the expression of DNMT3A in CA1 after tGCI with or without HPC.
2023-01-18 | GSE163299 | GEO
Project description:Comprehensive transcriptome analysis of osteoclasts with the SIK3 deletion and pterosin B treatment.
| PRJNA980570 | ENA
Project description:In mice and humans, sleep quantity of individuals are governed by genetic factors and exhibit age-dependent variations. However, the core molecular pathways and effector mechanisms that regulate sleep time in mammals remain unclear. Here, we characterize a major signaling pathway for transcriptional regulation of sleep quantity in mice by adeno-associated virus-mediated somatic genetics analysis. Adult brain chimeric-knockout of LKB1 kinase, an activator of AMPK-related protein kinase SIK3/SLEEPY, markedly reduces non-rapid eye movement sleep (NREMS) amount and delta power–a measure of sleep depth. Downstream of LKB1-SIK3 pathway, gain or loss-of-function of histone deacetylases HDAC4/5 in adult brain neurons causes bidirectional changes of NREMS amount and delta power. Phosphorylation of HDAC4/5 is regulated in relation to sleep need, and HDAC4 specifically regulates sleep amount in posterior hypothalamus. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signaling pathways targeting transcription modulators to regulate daily sleep amount and demonstrate utility of somatic genetics in mouse sleep research.
2022-09-18 | GSE182907 | GEO
Project description:Sleep deprivation (SD) in young adults is associated with metabolic, stress and cognitive responses that are also characteristic of brain aging. Given that sleep architecture changes with age, including increased fragmentation and decreased slow wave activity, it seems reasonable to investigate potential molecular relationships between SD and aging in brain tissue. Here, we tested the hypothesis that young rats exposed to 24 or 72 hour SD would respond with stress and aging-like shifts in brain hippocampal CA1 gene expression. SD animals showed blood corticosterone and weight changes consistent with a stress response. Microarray results, validated by Western blot and comparison to prior SD studies, pointed to disruptions in neurotransmission, sleep pressure signaling, and macromolecular synthesis. In a separate experiment, animals exposed to 24 or 72 hour novel environment stress recapitulated nearly one third of the SD transcriptional profile, particularly upregulated apoptotic and immune signaling pathways. Compared to aging (based on three previously published independent hippocampal aging studies), SD transcriptional profiles agreed for neurogenesis and energy pathways. However, immune signaling, glial activity, macromolecular synthesis and neuronal function all showed an SD profile that was, at least in part, opposed by aging. We conclude that while stress and SD have discrete molecular signatures, they do show a subset of highly similar changes. However, the same could not be said of aging and SD, where a similar subset of genes is changed, but in partially divergent directions. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel targets for future SD-countering therapeutics. Subjects: Male Fischer 344 rats (3-5 months old, Harlan, Indianapolis): 37 in cohort 1 and 32 in cohort 2. Subjects were assigned to one of 5 treatment groups: Home Cage-HC n =17; 24 hour sleep deprivation- 24SD n = 16; 72 hour sleep deprivation- 72SD n = 20; 24 hour novel environment stress- 24NES n = 10; 72 hour novel environment stress- 72NES n = 6. Cohorts 1 and 2 were combined for microarray analyses. Sleep Deprivation: The multiple platform modification (Coenen and van Luijtelaar, 1985) of the classic 'flower pot' (Mendelson et al., 1974) technique in which animals are placed on an elevated platform over water was used. Pairs of SD animals (cage mates) were sleep deprived for 24 or 72 hours. Novel Environment Stress (NES): NES animals were exposed to a novel environment, but were not constrained from sleeping. These NES animals paralleled the sleep deprivation exposure duration (24 hour- n = 10, and 72 hour- n = 6). Tissue Isolation: On the day that animals were removed from the SD chambers, they were anesthetized with CO2 gas and decapitated. Brains were removed and immediately placed in oxygenated artificial cerebrospinal fluid (aCSF) containing (in mM) 114NaCl, 2.5 KCl, 2MgCl2, 30 NaHCO3, 10 Glucose and 2.2CaCl2. Hippocampi were dissected as described previously (Blalock et al., 2003; Kadish et al., 2009). Briefly, dissected hippocampi were immersed in 0C oxygenated aCSF and placed on a chilled glass petri dish. The CA1 region was dissected along the long axis of the hippocampus. CA1 tissue was flash frozen and stored at -80C until further use. Microarray Protocol: GCOS quality control measures of background signal (74.9 ± 2.1 cohort 1; 59.8 ± 2.3 cohort 2) and RawQ (2.3 ± 0.1 cohort 1; 1.9 ± 0.1 cohort 2), as well as a chip x chip correlation matrix of signal intensity data pointed to a global decrease in background signal intensity in Cohort 2. To control for this, each gene expression values for HC, 24SD and 72SD was standardized separately within cohort 1 and cohort 2, and then the two cohorts were combined. This retained the variability of each cohort, but removed the 'cohort effect' from the data. Pre-statistical filtering retained 'A' grade probe sets that were uniquely annotated (Affymetrix, June 2011) with gene symbols and had at least 6 presence calls across all 71 chips. This criterion was selected based on factorial analysis demonstrating < 5% probability of 6 or more chips being rated present for a given probe set by chance (Blalock, unpublished observations).
2012-07-16 | E-GEOD-34424 | biostudies-arrayexpress