Metabolic control over mTOR dependent diapause-like state
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600822 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10875480.fastq.gz | Fastqsanger.gz | |||
| SRR10875481.fastq.gz | Fastqsanger.gz | |||
| SRR10875482.fastq.gz | Fastqsanger.gz | |||
| SRR10875483.fastq.gz | Fastqsanger.gz | |||
| SRR10875484.fastq.gz | Fastqsanger.gz |
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Project description:Regulation of embryonic diapause, dormancy that interrupts the tight connection between develop- mental stage and time, is still poorly understood. Here, we characterize the transcriptional and metabolite profiles of mouse diapause embryos and identify unique gene expression and metabolic signatures with activated lipolysis, glycolysis, and metabolic pathways regulated by AMPK. Lipolysis is increased due to mTORC2 repression, increasing fatty acids to support cell survival. We further show that starvation in pre-implantation ICM-derived mouse ESCs induces a reversible dormant state, transcriptionally mimicking the in vivo diapause stage. During starvation, Lkb1, an upstream kinase of AMPK, represses mTOR, which induces a revers- ible glycolytic and epigenetically H4K16Ac-negative, diapause-like state. Diapause furthermore activates expression of glutamine transporters SLC38A1/2. We show by genetic and small molecule inhibitors that glutamine transporters are essential for the H4K16Ac-negative, diapause state. These data sug- gest that mTORC1/2 inhibition, regulated by amino acid levels, is causal for diapause metabolism and epigenetic state.
2020-01-14 | GSE143494 | GEO
Project description:Regulation of embryonic diapause, dormancy that interrupts the tight connection between developmental stage and time, is still poorly understood. Here, we characterize the transcriptional and metabolite profiles of mouse diapause embryos and identify unique gene expression and metabolic signatures with activated lipolysis, glycolysis, and metabolic pathways regulated by AMPK. Lipolysis is increased due to mTORC2 repression, increasing fatty acids to support cell survival. We further show that starvation in pre-implantation ICM-derived mouse ESCs induces a reversible dormant state, transcriptionally mimicking the in vivo diapause stage. During starvation, Lkb1, an upstream kinase of AMPK, represses mTOR, which induces a reversible glycolytic and epigenetically H4K16Ac-negative, diapause-like state. Diapause furthermore activates expression of glutamine transporters SLC38A1/2. We show by genetic and small molecule inhibitors that glutamine transporters are essential for the H4K16Ac-negative, diapause state. These data suggest that mTORC1/2 inhibition, regulated by amino acid levels, is causal for diapause metabolism and epigenetic state.
| S-EPMC7204393 | biostudies-literature
Project description:Cultured pluripotent stem cells are a cornerstone of regenerative medicine due to their ability to give rise to all cell types of the body. While pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a very transient state in vivo, lasting 2-3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavorable conditions. Diapause is a strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that inhibition of mechanistic target of rapamycin (mTor), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent to give rise to embryonic stem (ES) cells and mice. We show that both natural diapause blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTor activity, translation and transcription. In addition, pausing can be induced directly in cultured ES cells and sustained for weeks in the absence of cell death or deviations from cell cycle distributions. We show that paused ES cells remain pluripotent, display a remarkable global suppression of transcription, and maintain a gene expression signature of diapaused blastocysts. These results allow for the first time the sustained suspension of development of a mammalian embryo in the laboratory, and shed light on the regulation of diapause and the origins of ES cells. Our findings have important implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and aging.
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Project description:Adult reproductive diapause is a powerful overwintering strategy for many continental insect species including bumblebees, which enables queens to survive several months through harsh winter conditions and then build new beehives in the following spring. There are few reports regarding the molecular regulatory mechanism of reproductive diapause in Bombus terrestris, which is an important pollinators of wild plants and crops, and our previous researches identified the conditions for reproductive diapause of year-round mass rearing. Here, we performed combined RNA sequencing transcriptomics and quantitative proteomic analyses in different development phases relate to reproductive diapause. According to the overall analysis, we found these differentially expressed proteins/genes act in the citrate cycle, insect hormone biosynthesis, insulin and mTOR signalling pathway. To get better sense of the reproductive diapause regulated mechanism, some genes regulated JH synthesis, insulin/ TOR signal pathway were detected, the BtRheb, BtTOR, BtVg and BtJHAMT had lower expression levels in diapause queens, and the JH III titers levels and some metabolic enzymes activities were significantly up-regulated in found post-diapause queens. After microinjected insulin-like peptides (ILPs) and JH analog (JHA), some indicators shows the significantly changes of hormones, cold tolerance substances, metabolic enzymes and reproduction. Along with other related researches, a reproductive diapause regulated model during B. terrestris year-round mass rearing process was establishment. This study contribute to a comprehensive view and the molecular regulate mechanism of productive diapause in eusocial insect.
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Project description:The most common ladybird beetle, Coccinella septempunctata L., is an excellent predator of crop pests such as aphids and white flies, and it shows a wide range of adaptability, a large appetite and a high reproductive ability. In this study, we collected female adults in three different states, i.e., non-diapause, diapause and diapause termination, for transcriptome sequencing. The experimental insects consisted of three different states as follows: Non-diapause female insects were reared at 24±1°C, with a RH of 70±10% and a 16:8 h light: dark (L: D) photoperiod and collected after their first oviposition. Female adults in diapause were reared at 18±1°C at an RH of 70±10% and a 10:14-h (L:D) photoperiod. The experimental diapause insects were collected after 30 days. Diapause-terminated adults were transferred to another climatic cabinet with the 30-day diapause insects and reared under the same conditions as the non-diapause insects. After their first oviposition, the female insects were collected and stored at -80°C. Three biological replicates per treatment (non-diapause, diapause, diapause-terminated) were sequenced using Illumina HiSeq 2500.
2016-06-01 | E-GEOD-75645 | biostudies-arrayexpress
Project description:Dormancy is a key feature of stem cell function in adult tissues as well as embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state is not known. Here we show that microRNA activity, which is normally dispensable for pre-implantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in loss of pluripotency and embryo collapse. Through tissue-specific small RNA profiling of single embryos and computational analyses of miRNA targets, we identified the miRNA-protein network of diapause. Individual miRNA function contributes to combinatorial regulation by the network of most notably RNA processing and chromatin modifier proteins. Without miRNAs, multiple nuclear and cytoplasmic bodies show aberrant expression and structure in normal ESCs and fail to reorganize in response to stress. We find extensive alternative splicing in wild-type, but not miRNA-deficient ESCs, of cell cycle and metabolic regulators. Our results reveal that miRNAs are critical for the transcriptional and structural rewiring of pluripotent cells in response to stress and to establish dormancy in the pluripotent state.
2024-03-26 | PXD044550 | Pride
Project description:Gene expression microarray experiment comparing differential expression across a developmental and metabolic trajectory of diapause termination. Six phenotypes representing 6 developmental time points, four replicate individuals for each phenotype, four competitve hybridizations for each of six phenotypic comparisons. Each individual was hybridized up to 3 times, each in a separate phenotypic comparison. Phenotypes: 24Fridge = early diapause (24 hours after transfer from fridge to 24C) LateDia = late diapause (2 weeks after transfer from fridge to 24C) Break24 = 24 hours after initial metabolic rate increase Break48 = 48 hours after initial metabolic rate increase Plat = in the metabolic rate plateau PostPlat = in the final, exponential phase of metabolic rate increase
2011-09-30 | E-GEOD-30785 | biostudies-arrayexpress
Project description:The most common ladybird beetle, Coccinella septempunctata L., is an excellent predator of crop pests such as aphids and white flies, and it shows a wide range of adaptability, a large appetite and a high reproductive ability. In this study, we collected female adults in three different states, i.e., non-diapause, diapause and diapause termination, for transcriptome sequencing.
2016-06-01 | GSE75645 | GEO
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Project description:Embryonic diapause is a widely occurring evolutionary adaptation phenomenon in animals. Artemia is one of the classic animal models for diapause research. The current studies of Artemia diapause mainly focus on the induction and maintenance of the embryonic diapause, but there is little research on the molecular regulatory mechanism of Artemia embryonic diapause termination (EDT) and embryonic reactivation. Here the gene expression of Artemia cyst in diapause stage and 5 hours after embryonic diapause termination (EDT), which is in post-diapause stage were tested by ATAC-seq to analyze the mechanism of signal regulation involved in Artemia EDT at the molecular level.
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