Bulk mRNA-seq of Inpp5e mutant embryonic cortex against wild-type controls
Ontology highlight
ABSTRACT:
INSTRUMENT(S): n/a, Illumina NovaSeq 6000
ORGANISM(S): Mus musculus
SUBMITTER: Thomas Theil
PROVIDER: E-MTAB-14015 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Primary cilia act as antennas in cell-cell signalling and are crucial for nervous system development. We explored their role in the development of the human cerebral cortex using organoids defective for the ciliary gene INPP5E. We investigated the transcription profile of control and INPP5ED477N/D477N mutant organoids at D25.
2022-06-06 | E-MTAB-11437 | biostudies-arrayexpress
Project description:Here we performed a ChIP-seq experiment on a sample of ventral telencephalon from E14.5 embryos. This resulted in the generation of a genome-wide map of Ascl1 binding to chromatin.
2021-07-03 | E-MTAB-9751 | biostudies-arrayexpress
Project description:Heterogeneous astrocyte populations are defined by diversity in cellular environment, progenitor identity or function. Yet, little is known about the extent of the heterogeneity and how this diversity is acquired during development. We used SILAC and quantitative proteomics to characterise primary murine telencephalic progenitor cells from FOXG1 (forkhead box G1)-cre driven Tgfbr2 (transforming growth factor beta receptor 2) knockout mice and identified differential protein expression of the astrocyte proteins GFAP (glial fibrillary acidic protein) and MFGE8 (milk fat globule-EGF factor 8). Biochemical and histological investigations revealed distinct populations of astrocytes in the dorsal and ventral telencephalon marked by GFAP or MFGE8 protein expression. The two subtypes differed in their response to TGFβ-signalling. Impaired TGFβ-signalling affected numbers of GFAP-astrocytes in the ventral telencephalon. In contrast, TGFβ reduced MFGE8 expression in astrocytes deriving from both regions. Additionally, lineage tracing revealed that both GFAP and MFGE8 astrocyte subtypes derived partly from FOXG1-expressing neural precursor cells.
2022-03-02 | PXD005072 | Pride
Project description:Cilia and flagella are dynamicallyregulatedduring development and differentiation. Coordination of temporal and spatial transcription regulators are essential for ciliogenesis. We here report that XAP5 and XAP5L are two conserved pairs of antagonistic transcription regulators that control ciliary transcriptional programs during spermatogenesis. Male mice lacking either XAP5 or XAP5L display infertility, as a result of meiotic prophase arrest and sperm cilia malformation, respectively. XAP5 positively regulates the ciliary gene expression by activating the key regulators including FOXJ1 and RFX families during the early stage of spermatogenesis. In contrast, XAP5L negatively regulates the expression of ciliary genes via repressing these ciliary transcription factors during the spermiogenesis stage. Taken together, our data provide new insights into the mechanisms by which temporal and spatial transcription regulators are coordinated to control ciliary transcriptional programs during spermatogenesis.
2023-07-06 | GSE236388 | GEO
Project description:Cilia are organelles specialized for movement and signaling. To infer when during animal evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from three organisms: sea urchins, sea anemones and choanoflagellates. From these ciliomes, we identified 437 high confidence ciliary candidate proteins conserved in mammals, including known regulators of Hh, GPCR and TRP channel signaling. The phylogenetic profiles of their ciliary association indicate that the Hh and GPCR pathways were linked to cilia before the origin of bilateria and TRP channels before the origin of animals. We demonstrated that some of the candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein that we identified in the cilia of all three organisms. In animals, ENKUR is expressed by cells with motile cilia, ENKUR localizes to cilia in diverse organisms and, in both Xenopus laevis and mice, ENKUR is required for patterning the left/right axis. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to Hh, GPCR and TRP channel signaling, and uncovers a novel ciliary protein that controls vertebrate development and human disease.
2019-12-16 | PXD006632 | Pride
Project description:We performed whole genome gene expression profiling in bronchial biopsies from PCD patients. We used the Quality Threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature search showed that 16250 genes in this cluster were known cilia genes, strongly indicating that the remaining 21022 genes were likely to be new cilia genes. The tissue expression pattern of the 210 new cilia genes and the 162 known genes was consistent with the presence of motile cilia in a given tissue. Analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups. Total RNA obtained from 6 primary ciliary dyskinesia patients and 9 control individuals
2015-02-24 | E-GEOD-25186 | biostudies-arrayexpress
Project description:Cilia are essential organelles that protrude from the cell body. Cilia are made of a microtubule-based structure called the axoneme. In most types of cilia, the ciliary tip is distinct from the rest of the cilium. By analysing Tetrahymena thermophila cells lacking a ciliary tip-enriched protein CEP104/FAP256 by mass spectrometry, we discovered candidates for the central pair cap complex and explained the potential functions of CEP104/FAP256. These data provide new insights into the function of the ciliary tip and the mechanisms of ciliary assembly and length regulation.
2023-09-01 | PXD042582 | Pride
Project description:Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. As cilia are diffusion barrier-gated subcellular compartments, their protein components are thought to come from the cell body through intraflagellar transport or diffusion. Here we show that cilia locally synthesize proteins to maintain their ultrastructure and functions. Multicilia of mouse ependymal cells were abundant in ribosomal proteins, translation initiation factors, and RNA, including 18S rRNA and tubulin mRNA. The cilia actively generated nascent peptides, including those of tubulin. FMRP, an RNA-binding component of messenger ribonucleoprotein granules critical for local translation, was concentrated in ciliary central lumen. Its depletion by RNAi impaired ciliary nascent peptide production and induced multicilia degeneration. Expression of exogenous FMRP, but not an isoform tethered to mitochondria, rescued the degeneration defects. Therefore, local translation defects in cilia might contribute to the pathology of ciliopathies and other diseases such as Fragile X syndrome.
2021-10-19 | GSE179935 | GEO
Project description:Astrocyte diversity is greatly influenced by local environmental modulation. In this study, we analyzed how primary ciliary signaling modulates astrocyte subtype-specific maturation and accessed the impact of ciliary deficient astrocytes on neuronal programs and behaviours. Comparative single-cell transcriptomics revealed that primary cilia mediate canonical Shh signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.
2024-01-24 | GSE253640 | GEO
Project description:Primary cilia are microtubule based sensory organelles that protrude from almost every cell type. Their membrane contains highly specialized receptors important for receiving and processing extracellular signals, which enables them to regulate several signalling pathways. A recently discovered characteristic is that cilia are also able to release extracellular vesicles (EVs) from the ciliary membrane. Since EVs have been shown to exert numerous functions in physiology and pathology, these findings have the potential to dramatically alter our understanding of how the primary cilium is able to regulate various signalling pathways in development and disease. In our study we focused on the release of EVs from a ciliated kidney cell line. Using control and mutant cell lines, in which ciliary trafficking was disrupted, we observed that loss of primary cilia function leads to altered EV secretion and composition in NTA (Nanoparticle Tracking Analysis) and Western blot. Cilia mutant cells released more small EVs compared to control, and their composition was also changed between mutant and control. Protein identification via mass spectrometry identified both cilia- as well as WNT signalling-associated proteins and miRNA sequencing determined WNT-related miRNAs, which were differentially expressed in small EVs isolated from the cilia mutant cell line. Because of the presence of differentially expressed WNT related molecules in these small EVs, we tested whether this would have an effect on the WNT activity of recipient cells. We observed that small EVs secreted from cilia mutant cells differentially modulated the WNT response in recipient cells compared to control. Our results highlight a possible new small EV-dependent ciliary signalling mechanism, since deficient primary cilia lead to a change in EV secretion, resulting in an altered signal transduction. These results provide us with new insights into ciliopathy disease pathogenesis.
2021-07-19 | GSE153227 | GEO