ChICseq analysis of active and repressive histone modifications in intestinal and non-intestinal C. elegans cells [ChIC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE304344 | GEO | 2025/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:Endomitosis is a non-canonical cell cycle in which cells undergo all four phases of a canonical cell cycle (G1, S, G2 and M), but do not initiate or complete cytokinesis during M phase. To identify the transcriptional differences between endomitosis and canonical cell cycles in C. elegans, we isolated cells from L1 larvae of a strain expressing intestinal-specific mCherry (elt-2p::mCherry-PH-P2A-H2B-mCherry) grown for 6 hours at 20ºC. We sorted intestinal and non-intestinal cells both with a 4N DNA content by FACS based on the mCherry expression and the Hoechst-34580 profile. We performed RNA-seq in intestinal (3 replicates) and non-intestinal cells (3 replicates) and differential gene expression analysis to identify the genes that are upregulated or downregulated in intestinal endomitosis compared to canonical cell cycles.
2025-08-02 | GSE304329 | GEO
Project description:The canonical mitotic cell cycle coordinates cell growth, DNA replication, centriole duplication and cytokinesis to generate two cells from one. In certain contexts, such as in mammalian trophoblast giant cells or hepatocytes, cells employ cell cycle variants like the endocycle or endomitosis to increase DNA content without undergoing cytokinesis. Multiciliated cells, found in the mammalian airway, brain ventricles and reproductive tracts, generate hundreds of centrioles during differentiation, each of which extend a motile cilium. We found that multiciliated cells utilize a variant of the cell cycle, which we refer to as the multiciliation cycle. The multiciliation cycle redeploys much of the mitotic cell cycle regulatory framework, including cell division kinases (CDKs) and cyclins, to generate hundreds of centrioles without undergoing DNA synthesis or cytokinesis. Unlike the mitotic cycle, a transcriptional repressor, E2F7, is upregulated during the multiciliation cycle. E2F7 directly represses genes encoding DNA synthesis machinery during the multiciliation cycle. Loss of E2F7 results in aberrant DNA synthesis and disruption of centriole biogenesis in differentiating multiciliated cells. Thus, multiciliation is coordinated by a variant cell cycle that uses E2F7 to uncouple centriole synthesis from DNA replication.
2024-03-30 | GSE228108 | GEO
Project description:The canonical mitotic cell cycle coordinates cell growth, DNA replication, centriole duplication and cytokinesis to generate two cells from one. In certain contexts, such as in mammalian trophoblast giant cells or hepatocytes, cells employ cell cycle variants like the endocycle or endomitosis to increase DNA content without undergoing cytokinesis. Multiciliated cells, found in the mammalian airway, brain ventricles and reproductive tracts, generate hundreds of centrioles during differentiation, each of which extend a motile cilium. We found that multiciliated cells utilize a variant of the cell cycle, which we refer to as the multiciliation cycle. The multiciliation cycle redeploys much of the mitotic cell cycle regulatory framework, including cell division kinases (CDKs) and cyclins, to generate hundreds of centrioles without undergoing DNA synthesis or cytokinesis. Unlike the mitotic cycle, a transcriptional repressor, E2F7, is upregulated during the multiciliation cycle. E2F7 directly represses genes encoding DNA synthesis machinery during the multiciliation cycle. Loss of E2F7 results in aberrant DNA synthesis and disruption of centriole biogenesis in differentiating multiciliated cells. Thus, multiciliation is coordinated by a variant cell cycle that uses E2F7 to uncouple centriole synthesis from DNA replication.
2024-03-30 | GSE245742 | GEO
Project description:The canonical mitotic cell cycle coordinates cell growth, DNA replication, centriole duplication and cytokinesis to generate two cells from one. In certain contexts, such as in mammalian trophoblast giant cells or hepatocytes, cells employ cell cycle variants like the endocycle or endomitosis to increase DNA content without undergoing cytokinesis. Multiciliated cells, found in the mammalian airway, brain ventricles and reproductive tracts, generate hundreds of centrioles during differentiation, each of which extend a motile cilium. We found that multiciliated cells utilize a variant of the cell cycle, which we refer to as the multiciliation cycle. The multiciliation cycle redeploys much of the mitotic cell cycle regulatory framework, including cell division kinases (CDKs) and cyclins, to generate hundreds of centrioles without undergoing DNA synthesis or cytokinesis. Unlike the mitotic cycle, a transcriptional repressor, E2F7, is upregulated during the multiciliation cycle. E2F7 directly represses genes encoding DNA synthesis machinery during the multiciliation cycle. Loss of E2F7 results in aberrant DNA synthesis and disruption of centriole biogenesis in differentiating multiciliated cells. Thus, multiciliation is coordinated by a variant cell cycle that uses E2F7 to uncouple centriole synthesis from DNA replication.
2024-03-30 | GSE245381 | GEO
Project description:The canonical mitotic cell cycle coordinates cell growth, DNA replication, centriole duplication and cytokinesis to generate two cells from one. In certain contexts, such as in mammalian trophoblast giant cells or hepatocytes, cells employ cell cycle variants like the endocycle or endomitosis to increase DNA content without undergoing cytokinesis. Multiciliated cells, found in the mammalian airway, brain ventricles and reproductive tracts, generate hundreds of centrioles during differentiation, each of which extend a motile cilium. We found that multiciliated cells utilize a variant of the cell cycle, which we refer to as the multiciliation cycle. The multiciliation cycle redeploys much of the mitotic cell cycle regulatory framework, including cell division kinases (CDKs) and cyclins, to generate hundreds of centrioles without undergoing DNA synthesis or cytokinesis. Unlike the mitotic cycle, a transcriptional repressor, E2F7, is upregulated during the multiciliation cycle. E2F7 directly represses genes encoding DNA synthesis machinery during the multiciliation cycle. Loss of E2F7 results in aberrant DNA synthesis and disruption of centriole biogenesis in differentiating multiciliated cells. Thus, multiciliation is coordinated by a variant cell cycle that uses E2F7 to uncouple centriole synthesis from DNA replication.
2024-03-30 | GSE228109 | GEO
Project description:TO explore role of DGCR8, a essential factor in canonical microRNAs biogenesis, in intestinal epithelial regeneration, we performed gene expression profiling analysis using data obtained from RNA-seq of intestinal organoids, intesitnal stem cells, and crypts from mice following 5-FU administration. To further investigate which microRNA was responsible for intestinal regeneration, we also performed small RNA sequencing with intestinal stem cells and intestinal epithelia cells.
2023-12-13 | GSE230172 | GEO
Project description:The alternative (non-canonical) nuclear factor-kappa B (NF-κB) signalling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline Nfkb2 deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, such as azoxymethane/dextran sulfate sodium (DSS)-induced colitis-associated cancer and lipopolysaccharide (LPS)-induced small intestinal epithelial apoptosis. However, the common underlying protective mechanisms are not yet fully understood. Here we applied RNA sequencing and identified a B-lymphocyte defect as the major signature in the small intestinal mucosa of naïve adult Nfkb2-/- mice. Proteomics analysis also revealed a dramatic decrease in small intestinal immunoglobulin A levels, and this was validated by quantitative ELISA in both small intestinal lysates and serum. Moreover, the numbers of IgA-producing, CD138+ve plasma cells were also reduced in the lamina propria of the small intestinal villi of Nfkb2-/- mice. This phenotype was even more striking in the small intestinal mucosa of RelB-/- mice, although these mice were equally sensitive to LPS-induced intestinal apoptosis as their RelB+/+ wild-type counterparts. Therefore, p52 deficiency offers resistance to LPS-induced intestinal apoptosis and appears to regulate the plasma cell population within the gut.
2022-07-31 | E-MTAB-11018 | biostudies-arrayexpress
Project description:A detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required for better treatment options for a variety of chronic intestinal diseases, however, current models of ISC lineage hierarchy and segregation are still under debate. Here we report the identification of Lgr5+ ISCs that express Flattop (Fltp), a Wnt/planar cell polarity (PCP) reporter and effector gene. Functional analysis and lineage tracing revealed that Wnt/PCP-activated Fltp+ ISCs are primed towards either the enteroendocrine or Paneth cell lineage in vivo, while retaining self-renewal and multi-lineage capacity in vitro. Surprisingly, canonical Wnt/beta-catenin- and non-canonical Wnt/PCP-activated Lgr5+ ISCs are indistinguishable by the expression of stem-cell signature or secretory lineage-specifying genes, suggesting that lineage priming and cell-cycle exit is triggered at the post-transcriptional level by polarity cues and a switch of canonical to non-canonical Wnt signalling. Pseudotemporal ordering of targeted single-cell gene expression data allowed us to delineate the ISC differentiation path into enteroendocrine and Paneth cells. Strikingly, both lineages are directly recruited from ISCs via unipotent transition states, excluding the existence of formerly predicted bi- or multipotent secretory progenitors. Transitory cells that mature into Paneth cells are defined by label-retention and co-expression of stem cell and secretory lineage genes, indicating that these cells are the previously described Lgr5+ label-retaining cells (LRCs). Taken together, we identified the Wnt/PCP pathway as a new niche signal and polarity cue regulating stem cell fate. Active Wnt/PCP signalling represents one of the earliest events in ISC lineage priming towards the Paneth and enteroendocrine cell fate, preceding lateral inhibition and expression of secretory lineage-specifying genes. Thus, our findings provide a better understanding of the niche signals and redefine the mechanisms underlying ISC lineage hierarchy and segregation. Here we establish the Wnt/Planar cell polarity (PCP) gene Flattop (Fltp) as a unique marker for intestinal LRCs and their distinct secretory fate. We show that Fltp+ cells are characterized by a combined stem cell and secretory gene signature. A subset of Fltp+ cells is classified by label-retention and predominantly locates at position +4, indicative of quiescent stem cells. Strikingly, Fltp+ LRCs are specified by Wnt/PCP signaling in contrast to actively cycling stem cells that rely on the canonical Wnt/β-catenin pathway. In mice with disturbed Wnt/PCP signaling, the differentiation of enteroendocrine cells from LRCs is impaired. These findings establish Fltp as a novel marker for intestinal LRCs and implicate Wnt/PCP signaling in cell-cycle exit and commitment of ISCs to the secretory lineage. Taken together, we not only provide a marker to study LRCs in homeostatic and diseased conditions, but also identify the Wnt/PCP signaling pathway as a therapeutic target for colorectal cancer and metabolic disease.
2020-09-11 | GSE72112 | GEO
Project description:The MSI2 RNA binding protein has recently emerged as a potent oncogene playing key roles in hematopoietic stem cell homeostasis and malignant hematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss of function abrogates colorectal cancer cell growth. We thus examined the oncogenic consequences of MSI2 gain of function in the intestinal epithelium with a drug inducible mouse model. Strikingly, MSI2 induction alone was sufficient to phenocopy the majority of morphological and molecular consequences of acute loss of the APC tumor suppressor in the intestinal epithelium. We demonstrate that this phenotype is independent of both the activation of the other oncogenic Musashi family member, Msi1, and of canonical Wnt pathway activation. Transcriptome-wide RNA-binding analysis indicates that MSI2 acts as a pleiotropic inhibitor of known intestinal tumor suppressors including Lrig1, Bmpr1a, Cdkn1a, and Pten. Finally, we demonstrate that inhibition of the PDK-AKT-mTORC1 axis downstream of Pten rescues oncogenic consequences of MSI2 induction. Taken together, our findings identify MSI2 as a central component in an unappreciated oncogenic pathway promoting intestinal transformation. 2 wild-type samples, 2 TRE-Msi2 samples
2014-12-20 | E-GEOD-64388 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. The canonical mitotic cell cycle coordinates DNA replication, centriole duplication and cytokinesis to generate two cells from one1. Some cells, such as mammalian trophoblast giant cells, use cell cycle variants like the endocycle to bypass mitosis2. Differentiating multiciliated cells, found in the mammalian airway, brain ventricles and reproductive tract, are post-mitotic but generate hundreds of centrioles, each of which matures into a basal body and nucleates a motile cilium3,4. Several cell cycle regulators have previously been implicated in specific steps of multiciliated cell differentiation5,6. Here we show that differentiating multiciliated cells integrate cell cycle regulators into a new alternative cell cycle, which we refer to as the multiciliation cycle. The multiciliation cycle redeploys many canonical cell cycle regulators, including cyclin-dependent kinases (CDKs) and their cognate cyclins. For example, cyclin D1, CDK4 and CDK6, which are regulators of mitotic G1-to-S progression, are required to initiate multiciliated cell differentiation. The multiciliation cycle amplifies some aspects of the canonical cell cycle, such as centriole synthesis, and blocks others, such as DNA replication. E2F7, a transcriptional regulator of canonical S-to-G2 progression, is expressed at high levels during the multiciliation cycle. In the multiciliation cycle, E2F7 directly dampens the expression of genes encoding DNA replication machinery and terminates the S phase-like gene expression program. Loss of E2F7 causes aberrant acquisition of DNA synthesis in multiciliated cells and dysregulation of multiciliation cycle progression, which disrupts centriole maturation and ciliogenesis. We conclude that multiciliated cells use an alternative cell cycle that orchestrates differentiation instead of controlling proliferation.
2024-03-29 | GSE228110 | GEO