Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Calorie restriction governs intestinal epithelial regeneration through cell autonomous regulation of mTORC1 in reserve stem cells

ABSTRACT: Here, we show that CR enhances regenerative capacity of the intestinal epithelium as a result of increased number of reserve ISCs. We observe that precise regulation of mechanistic target of Rapamycin complex 1 (mTORC1) signaling plays a significant role in regulation of sensitivity of reserve intestinal stem cells to injury and that premature activation of mTORC1 signaling through nutrient modulation, at the time of damage, leads to poor regeneration outcome. These data delineate a critical role for mTORC1 signaling in epithelial regeneration and inform clinical strategies based on nutrient modulation of mTORC1 activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE109002 | GEO | 2018/01/15

SECONDARY ACCESSION(S): PRJNA429386

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Calorie restriction governs intestinal epithelial regeneration through cell autonomous regulation of mTORC1 in reserve stem cells

Project description:Calorie restriction governs intestinal epithelial regeneration through cell autonomous regulation of mTORC1 in reserve stem cells

| PRJNA429386 | ENA

RNA seq dataset of parental and reserve cells (FRCs Cycle 1 and SRCs Cycle 3)

Project description:Loss of regenerative capacity during ex vivo expansion of muscle stem cells hampers the development of cell-based therapies for skeletal muscle disorders. Here, we developed a method to isolate regenerative reserve cell fractions from expanded murine primary cultures using differential adhesion properties and the induction of subsequent cycles of proliferation and differentiation. Fast-adhering reserve cells (FRCs) were enriched for cells expressing myogenin and contributed efficiently to muscle regeneration following transplantation in immunodeficient hosts. Slow adhering reserve cells (SRCs) generated higher number of PAX7+ cells under differentiating conditions and predominantly regenerated muscle after a secondary injury, suggesting engraftment as muscle stem cells. Transcriptomic analysis revealed that FRCs were enriched for markers of myogenic differentiation, while SRCs were characterized by a distinctive set of cell-adhesion genes. Overall, reserve cells provide a valuable source for the study and identification of molecular determinants of regeneration using ex vivo-expanded muscle cells.

2020-11-10 | GSE161075 | GEO

The transcriptome of human oocytes is related to age and ovarian reserve.

Project description:Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman’s age is correlated to lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activation (EGA) relies on maternal RNA and proteins. Age and ovarian reserve both affects oocyte developmental competence, however, their relative importance in this process are difficult to tease out, as ageing is accompanied by a decrease in ovarian reserve. Oocytes store large quantities of RNA, including several noncoding transcripts (ncRNAs) involved in early development transcription and translation modulation. Despite the central role of ncRNAs in maternal to zygote transition, no characterization of the ncRNA transcriptome in human oocytes has been reported. This study aims at identifying how the human oocyte transcriptome changes across reproductive ages and ovarian reserve levels, with the goal of identifying candidate markers of developmental competence, and to assess the independent relevance of age and ovarian reserve in the changes of the transcriptome

2017-08-29 | GSE87201 | GEO

The regulation of reserve carbohydrate metabolism in S cerevisiae in response to nutrient availability

Project description:In Saccharomyces cerevisiae, glycogen and trehalose are important reserve carbohydrates that accumulate under nutrient limitation in batch cultures. An inherent draw-back of batch studies is that specific growth rate and substrate and product concentrations are variable over time and between cultures. The aim of this present study was to identify the nutritional requirements associated with high accumulation of reserve carbohydrates at a fixed specific growth rate (0.10 h-1) in anaerobic chemostat cultures that were limited by one of five different nutrients (carbon, nitrogen, sulfur, phosphorus or zinc). Reserve carbohydrates accumulation is not a general response to nutrient limitation. Over the conditions tested, accumulation occurs essentially under nitrogen (and to a lesser extent carbon) limited conditions. This was confirmed by the transcriptional profile of the genes involved in trehalose biosynthesis. We show that the transcriptional induction of both glycogen and trehalose biosynthesis genes was to a large extent driven by the regulator Msn2/4. However, the main regulatory control of glycogen biosynthesis was post-translational. Under nitrogen limitation, the ratio of glycogen synthase over glycogen phosphorylase increased up to eight-fold, thus enabling an increased flux towards glycogen biosynthesis.

2009-08-20 | GSE15465 | GEO

Calorie Restriction Governs Intestinal Epithelial Regeneration through Cell-Autonomous Regulation of mTORC1 in Reserve Stem Cells.

Project description:Aging is a complex process associated with a decline in functionality of adult stem cells affecting tissue homeostasis and regeneration. Calorie restriction (CR) is the only experimental manipulation known to extend lifespan and reduce the incidence of age-related disorders across numerous species. These benefits are likely mediated, at least in part, through the preservation of stem cell function. Here, we show that CR enhances the regenerative capacity of the intestinal epithelium through preservation of an injury-resistant reserve intestinal stem cell (ISC) pool. Cell-autonomous activity of mechanistic target of rapamycin complex 1 (mTORC1) governs the sensitivity of reserve ISCs to injury. CR inhibits mTORC1 in these cells, protecting them against DNA damage, while mTORC1 stimulation, either genetically or through nutrient sensing, sensitizes reserve ISCs to injury, thus compromising regeneration of the epithelium. These data delineate a critical role for mTORC1 in epithelial regeneration and inform clinical strategies based on nutrient modulation.

| S-EPMC5919411 | biostudies-literature

Transcription profiling of Saccharomyces cerevisiae reveals the regulation of reserve carbohydrate metabolism in S cerevisiae in response to nutrient availability

2009-09-05 | E-GEOD-15465 | biostudies-arrayexpress

Let-7 coordinately suppresses components of the amino acid sensing pathway to induce autophagy

Project description:Macroautophagy (hereafter autophagy) is the major pathway by which macromolecules and organelles are degraded. Autophagy is regulated by the mTOR signaling pathway, which is the focal point for integration of metabolic information, with mTORC1 playing a central role in balancing biosynthesis and catabolism. Of the various inputs to mTORC1, the amino acid sensing pathway is among the most potent. Based upon transcriptome analysis of neurons subjected to nutrient deprivation, we identified let-7 as a microRNA capable of promoting neuronal autophagy. We found that let-7 activates autophagy by coordinately down-regulating the amino acid sensing pathway to prevent mTORC1 activation. Let-7 induced autophagy in the brain and greatly reduced protein aggregates in a lentivirus model of polyglutamine disease, establishing the physiological relevance of let-7 for in vivo autophagy modulation. Moreover, peripheral delivery of let-7 anti-miR repressed autophagy in muscle and white fat, suggesting that let-7 autophagy regulation extends beyond the CNS. Hence, let-7 plays a central role in nutrient homeostasis and proteostasis regulation in higher organisms. Using sets of wild-type C57BL/6J mice, we established primary cortical neuron cultures from P0 littermates, and cultured these neurons (n = 3 / set) in CM or NLM for 4 hrs.

2015-08-03 | E-GEOD-60452 | biostudies-arrayexpress

Sympathetic nerves regulate intestinal regeneration through IL22 signaling

Project description:The intestine is a barrier tissue whose epithelium has high intrinsic turnover rate; intestinal stem cells, in response to signals from the niche, self-renew and produce progeny that differentiate to fulfill the continuous demand for new epithelial cells that are continuously shed into the lumen. The intestine is innervated by a dense network of peripheral nerves that controls nutrient absorption, intestinal motility, and visceral pain sensation. However, the roles of neurons in regulating epithelial cell homeostasis or regeneration remain as yet undiscovered. Here we investigate the effects of gut-innervating sympathetic neurons on epithelial cell repair following irradiation (IR)-induced gut injury. We observed that sympathetic innervation density in the gut increases post IR, while chemical sympathetic denervation impairs gut regeneration. Combining single cell RNA-sequencing and in vivo experiments, we discovered that sympathetic neurons regulate gut regeneration through modulation of IL22 production in type 3 innate lymphoid cells (ILC3) downstream of 2-adrenergic receptor signaling. These results define a novel neuroimmune axis important for intestinal regeneration.

2023-08-18 | GSE214821 | GEO

Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury

Project description:The currently accepted intestinal epithelial cell organization model equates crypt base columnar (CBC) cells, marked by high levels of Lgr5 expression, with the intestinal stem cell (ISC). However, recent intestinal regeneration studies have uncovered limitations of the ‘Lgr5-CBC’ model, leading to two major views: one favoring the presence of a quiescent reserve stem cell population, the other calling for differentiated cell plasticity. To test if an alternative model may help reconcile these perspectives, we studied the hierarchical organization of crypt epithelial cells in an unbiased fashion, by combining high-resolution, single-cell profiling and lineage tracing in multiple transgenic mouse models. These show that Lgr5 is not a specific ISC marker; rather, cells located in the crypt isthmus, which include Lgr5low cells, comprise the ISCs that sustain tissue homeostasis. Following irradiation or intestinal injury, surviving ISCs and progenitors, but not differentiated cells, participate in intestinal regeneration, suggesting that neither de-differentiation nor reserve stem cell populations are drivers of intestinal regeneration. Our results provide a novel viewpoint for the intestinal crypt epithelium, in which ISCs localize to the crypt isthmus, and ISC potential is restricted to stem and progenitor cells.

2024-03-24 | GSE205229 | GEO

Constitutively Active Foxo3 in Oocytes Preserves Ovarian Reserve in Mice

Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice. Trangenic vs non-transgenic mice onto Foxo3+/- vs Foxo3-/- genotype

2013-06-08 | E-GEOD-45389 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data