Despite even large phenotypic differences among vertebrate groups, dentitions and jaws fit and function together, yet the genetic processes that orchestrate cranial and dental morphogenesis remain poorly understood. In the p63-/- mouse mutant, teeth but not jaws fail to form. This edentate mouse is a model with which to tease out genes important for odontogenesis but not jaw morphogenesis, and which may thus allow dentitions to change during development and evolution without necessarily affecting the jaw skeleton. With the working hypothesis that tooth and jaw development are autonomously controlled by discreet gene regulatory networks, we probed for genes crucial for tooth development only. Using gene expression microarray assays validated by quantitative reverse-transcription PCR, we contrasted expression in mandibular prominences at embryonic days (E) 10-13 among mice with normal lower jaw development and either normal (p63+/-, p63+/+) or arrested (p63-/-) tooth development. We predicted that expression of a suite of genes specific to odontogenesis would differ in the edentate mice. The p63-/- mice showed significantly different expression (fold change 1.5, -1.5; p0.05) of several genes, some of which are already reported to help regulate odontogenesis (e.g., p63, Osr2, Cldn3/4) and/or to be targets of p63 (e.g., Jag1/2, Fgfr2), others of which have no previously reported roles in odontogenesis or the p63 pathway (e.g, Fermt1, Cbln1, Pltp, Cxcl14, Krt8, and additional keratin and claudin family members). As expected, from E10-E13 few genes known to regulate mandible morphogenesis differed in expression between mouse strains. Thus this study links for the first time several genes to odontogenesis and/or the p63 signaling network. We propose that these genes act in a novel odontogenic network that is exclusive of lower jaw morphogenesis, and posit that this network evolved in oral, not pharyngeal, teeth.
Detangling the evolutionary developmental integration of dentate jaws: evidence that a p63 gene network regulates odontogenesis exclusive of mandible morphogenesis.
Specimen part
View SamplesGlioblastoma (GBM) patient-derived orthotopic xenografts (PDOXs) were derived from organotypic spheroids obtained from patient tumor samples. To detect whether gene expression profiles of GBM patient tumors are retained in PDOXs, we performed genome-wide transcript analysis by human-specific microarrays . In parallel, we analyzed GBM cell cultures and corresponding intracranial xenografts from stem-like (NCH421k, NCH644) and adherent GBM cell lines (U87, U251). PDOXs show a better transcriptomic resemblance with patient tumors than other preclinical models. The major difference is largely explained by the depletion of human-derived non-malignant cells.
Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β.
Specimen part, Disease, Disease stage, Treatment, Time
View SamplesWe describe here a male infant with a 100 kb de novo Xq28 deletion encompassing parts of the TMEM187 and MECP2 protein-coding genes and the IRAK1 protein-coding gene, as well as the MIR3202-1, MIR3202-2, and MIR718 RNA-coding genes. We analyzed the impact of human IRAK-1 deficiency on a genome-wide gene expression in human fibroblasts in response to TLR2/6, TLR4 agonists as well as to IL-1 and TNF-, using primary fibroblasts from healthy controls and IRAK-4-, MyD88- and MECP2-deficient patients for comparison.
Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.
No sample metadata fields
View SamplesLung alveolarization is a complex process that involves interactions between several cell types and leads to considerable increase in gas-exchange surface area. The step designated secondary septation includes elastogenesis from interstitial fibroblasts.
Gene expression profiling in lung fibroblasts reveals new players in alveolarization.
No sample metadata fields
View SamplesMolecular mechanisms that are responsible for the development of human skin epithelial cells are not completely understood so far. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSC) remains poor. Using an approach including RNA interference and high-throughput imaging of early epithelial cells, we could identify candidate kinases which are involved in skin epithelial differentiation. Among them, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors, increased the amount of generated keratinocytes and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input in the regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs.
Specimen part, Time
View SamplesThe ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies. The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action. Using the Affymetrix rat arrays (RAE230A), 6 control samples and 5 KD samples were run.
Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet.
No sample metadata fields
View SamplesThree different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.
Subject
View SamplesPurpose: Two secreted Toxoplasma proteins (GRA17 and GRA23) mediate the passage of small molecules between the host cytoplasm and the parasite-containing vacuole. This provides the first molecular explanation to how intracellular, vacuole-residing parasites in the phylum Apicomplexa, like Plasmodium, gain access to host nutrients. Methods: Mouse-derived Bone Marrow Macrophages were infected with Toxoplasma tachyzoites of either WT, dGRA17, dGRA23, or dGRA17rescue genetic background for 4 hours. Results: GRA23 gene expression levels are elevated in the dGRA17 strain but not vice versa. Conclusions: GRA17 and GRA23 are synergistically required for permeability of small molecules into the Toxoplasma parasitophorous vacuole. Overall design: Toxoplasma and Mouse gene expression profiles from BMDMs infected with either WT (control), dGRA17, gGRA23, or dGRA17rescue (control) tachyzoites were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at 4 hours post-infection.
The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole.
No sample metadata fields
View SamplesThe size and scope of microarray experiments continue to increase. However, datasets generated on different platforms or at different centres contain biases. Improved techniques are needed to remove platform- and batch-specific biases. One experimental control is the replicate hybridization of a subset of samples at each site or on each platform to learn the relationship between the two platforms. To date, no algorithm exists to specifically use this type of control. LTR is a linear-modelling-based algorithm that learns the relationship between different microarray batches from replicate hybridizations. LTR was tested on a new benchmark dataset of 20 samples hybridized to different Affymetrix microarray platforms. Before LTR, the two platforms were significantly different; application of LTR removed this bias. LTR was tested with six separate data pre-processing algorithms, and its effectiveness was independent of the pre-processing algorithm. Sample-size experiments indicate that just three replicate hybridizations can significantly reduce bias. An R library implementing LTR is available.
LTR: Linear Cross-Platform Integration of Microarray Data.
Sex
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