Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNAseq analysis of Xenopus laevis wildtype and emi2 mutant multiciliated cells during and post differentiation

ABSTRACT: Multiciliated cells (MCCs) form when progenitors massively expand centriole number, yielding the hundreds of basal bodies required to extend multiple motile cilia. This organelle biogenesis is promoted transcriptionally by Multicilin acting in a complex with the E2F transcription factors, which activates the expression of genes known to be involved required to form centrioles during the cell cycle, but also requires a cell cycle state required for the centrosome cycle. Multicilin also activates the expression of Emi2 (fbxo43) an inhibitor of the APC/C ubiquitin ligase. In Emi2 mutants, basal body formation during MCCl differentiation is blocked. RNAseq analysis is used to show that gene expression associated with MCC differentiation is upregulated normally in Emi2 mutants, but surprisingly is not downregulated when MCC differentiation is complete. Emi2 is required to promote the centrosomal cycle during MCC differentiation, but then also acts to turn off gene expression associated with centriole biogenesis in differentiated cells.

ORGANISM(S): Xenopus laevis

PROVIDER: GSE195635 | GEO | 2024/03/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Xenopus laevis

Project description:Multicilin drives centriole biogenesis via E2f proteins

| PRJNA255038 | ENA

Xenopus laevis

Project description:Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.

| PRJNA147733 | ENA

RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

Project description:A core pathophysiology underlying many respiratory diseases is multiciliated cell dysfunction leading to inadequate mucociliary clearance. Due to the prevalence and high variability of etiologies of MCC dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelium, however this does not apply to all cell types nor occur evenly across all cells in the same cell population. In this study we investigated we further investigate how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells we identify RBL2 as an inhibitor of the transcriptional activity of Multicilin. Both knockdown of RBL2 and phosphorylation of RBL2 driven by exposure to an air-liquid interface in the presence of Multicilin activated multiciliogenesis demonstrating a dynamic interaction regulating the differentiation of human airway epithelial cells. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases where mucociliary clearance is impeded.

2024-01-31 | GSE235682 | GEO

Identification of CDC20/CDC20B partners in HEK cells demonstrates that CDC20, but not CDC20B, interacts with multiple APC/C components

Project description:Multiciliated cells (MCCs) harbour dozens to hundreds of motile cilia, which beat in a synchronized and directional manner, thus generating hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation critically depends on the synthesis and release of numerous centrioles by specialized structures called deuterosomes. Little is known about the composition, organization and regulation of deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome-stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate specific cell division cycle 20B (CDC20B) gene, the host gene of microRNA-449abc. We show that the CDC20B protein associates to deuterosomes and is required for the release of centrioles and the subsequent production of cilia in mouse and Xenopus MCCs. CDC20B interacts with PLK1, which has been shown to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescued centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of a new biological function, deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules. A specific aim of this mass spectrometry experiment was to verify on immunoprecipitated protein complexes from CDC20 or CDC20B transfected HEK cells that CDC20, but not CDC20B, interacts with multiple APC/C components.

2019-04-03 | PXD010629 | Pride

Edf1 control multiciliated ependymel cell associated genes expression

Project description:The development and differentiation of Multiciliated ependymal cells are crucial for brain development, with defects leading to conditions such as congenital hydrocephalus. The differentiation of MCCs depends on a unique transcriptional program. Our study shows that Edf1, previously implicated as a transcriptional co-factor, is consistently expressed during MCC development and positively regulates key genes involved in multiciliogenesis and physiological functions.

2023-12-31 | GSE244940 | GEO

Airway mouse epithelial cells (mTECs) cultured at air-liquid interface

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

Single-cell RNA-sequencing of wildtype murine tracheal epithelial cells cultured at air-liquid interace for one, three, nine, and thirty-six days.

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

Single-cell RNA-sequencing of Ribociclib treated mTECs

2024-03-30 | GSE245381 | GEO

Single-cell RNA-sequencing of E2f7 knockout and wild-type littermate control murine tracheal epithelial cells cultured at air-liquid interace for seven days.

2024-03-30 | GSE228108 | GEO

E2F7-GFP binding sites in primary airway mouse epithelial cells (mTECs) cultured at air-liquid interface for three days.

2024-03-30 | GSE245742 | GEO