The goals of this study is to test whether NICD presence protects the RBPjk-null Hair Follicles by altering gene expression via association with other DNA binding proteins at P3, just before the conversion to TSLP-producing keratin cysts. Overall design: Methods: Skin samples were embedded in OCT. Sectioned at 20µm thickness. Dehydrated in EtOH, and equilibrated to Xylene before the LCM procedure. Laser capture was performed with Arcturus Veritas. Methods: ~100 hair follicles from Notch-null, PS-null, RBPjk-null and wild-type samples were pooled into 3 biological replicates for each genotype and subjected to RNA isolation followed by RNA-Seq. Conclusions: A total of 2047 genes were differentially expressed (=1.5 fold) in three or more biological replicates of Notch mutant hair follicles compared to wild-type controls (p-value<0.05). Unsupervised hierarchical clustering analysis failed to distinguish between the mutants.
The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development.
Cell line, Subject
View SamplesNotch1 deficient hair matrix keratinocytes have lower mitotic rates, resulting in smaller follicles with fewer cells. In addition, the ratio of melanocytes to keratinocytes is greatly reduced. Microarray was performed to study downstream mechanism of Notch1-deficiency
Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes.
No sample metadata fields
View SamplesPurpose: To use single-cell RNA-Seq analysis of nephron progenitors in order to determine transcrptional differences as nephron progenitors age. Methods: Using a combination of FACS sorting and a Fluidigm Single-cell auto-prep system, we generated high-throughput RNA-SEQ data of nephron progenitors during development Results: Single cells transcriptome profiling of nephron progenitors revealed progressive age-dependent changes with heterogeneity increasing in older populations. Overall design: 96-single cell transcriptomes were determined from nephron progenitors of e14.5, e18.5 and P0 using Cited1GFP transgenic animals
Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.
No sample metadata fields
View SamplesPurpose: To use RNA-Seq analysis of endothelial cell in various Notch1 alllels in order to determine transcrptional differencesas a consequence of Notch dose. Methods: Using a FACS sorting we generated high-throughput RNA-SEQ data of endothelials in various Notch1 alleles during development Results: Notch1 dose can alter gene expression in a subset of endothelial genes Overall design: RNA-Seq was performed on endothelial cells isolated at e9.5 from embryos with various Notch1 alleles including N1+/+, N1+/-, N1+/vg, N112/vg, N112/-
The intracellular domains of Notch1 and Notch2 are functionally equivalent during development and carcinogenesis.
No sample metadata fields
View SamplesThe 16p11.2 deletion and duplication syndromes have been associated with developmental delay and autism spectrum disorders, and a reciprocal effect on body mass index. Here we explored these links with new engineered mouse models carrying a deletion (Del/+) and duplication (Dup/+) of the whole 16p11.2 homologous Sult1a1-Spn region. On a pure genetic background, compared to wild-types, Del/+ mice carrying the deletion showed weight and adipogenesis deficits, hyperactivity, repetitive behaviors, and recognition memory deficits, whereas Dup/+ mice showed the opposite phenotypes and Del/Dup individuals displayed no changes. Alterations in social interaction were also observed in Del/+ and Dup/+ animals on a mixed genetic background.
Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.
Sex, Specimen part
View SamplesInjured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model. Hh signaling through FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. A pharmacological mimetic of TIMP3 blocked the conversion of FAPs into adipocytes, pointing to a strategy to combat fatty degeneration of skeletal muscle. We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury. Overall design: Transcriptomic profiling using RNAseq was performed on RNA derived from a bipotent, progenitor cell population, called fibro/adipogenic progenitors (FAPs), purified from tibialis anterior muscle 3 days post glycerol injury. Two populations of cells were sequenced, one from wild type muscle (FAP-ctrl) and another from cells in which cilia, using a floxed Ift88 allele, were conditionally deleted (FAP-no cilia). A total of five FAP-ctrl and 3 FAP-no cilia samples were used. The TruSeq Stranded Total RNA Library Prep Kit (Ilumina) was used to generate the library, which was subsequently sequenced using an Illumina 2500 SE 50bp platform and aligned to the GRCm38.78 whole genome using STAR RNAseq aligner. Individual read counts were normalized to the geometric mean read count across all samples using DEseq. Sequencing yielded ~314 million total reads with an average read depth of ~34.9 million reads per sample.
Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis.
Specimen part, Cell line, Subject
View SamplesTo determine if RU-486 would be effective as a chemopreventive agent, microarrays were used to analyse global gene expression changes in wild-type vs. MMTV-PAX8PPARg mice to determine their differential response to RU486
The chemopreventive effect of mifepristone on mammary tumorigenesis is associated with an anti-invasive and anti-inflammatory gene signature.
Specimen part, Treatment
View SamplesLow incubation temperature during early development negatively affects survival and related innate immune processes in zebrafish larvae exposed to lipopolysaccharide Overall design: Zebrafish embryos were collected from 28 °C, and divided into three temperature groups (24 °C, 28 °C, 32 °C) for incubation. At the first-feeding stage, larvae from each incubation temperature group were further split into three temperature groups in a full-factorial way for LPS challenge. In total, nine temperature groups (three incubation temperatures x three challenge temperatures) were generated. At 24 h post LPS challenge, mortality of larvae were recorded. Larvae originating from 24 °C incubation temperature group had higher mortality rate than larvae from the other two temperature groups. LPS-treated larvae from three temperature groups, incubation 24 °C x challenge 24 °C, incubation 24 °C x challenge 32 °C, and incubation 32 °C x challenge 24 °C, together with their respective control were chosen for transcriptomic analyses using mRNA sequencing. A total of 722 genes were determined differentially expressed (DEGs) by DESeq2 (adjusted p-value < 0.05) in LPS-challenged larvae compared to control, and 605 of them had a fold change greater than 1.5, including 294 DEGs (144 up-/150 down-regulated) in larvae incubated and challenged with LPS at 24 °C; 33 DEGs (20 up-/13 down-regulated) in larvae incubated at 32 °C and challenged at 24 °C; and 278 DEGs (190 up-/88 down-regulated) in larvae incubated at 24 °C and challenged at 32 °C. Larvae incubated and challenged with LPS at 24 °C had stimulated innate immune response compared to control, while they also showed down-regulated innate immune processes and genes. In larvae incubated at 32 °C and challenged at 24 °C, the innate immune processes were up-regulated in larvae exposed to LPS compared to control, and theses processes were even much stronger (with higher enrichment values) than larvae from incubation and challenge temperature of 24 °C. In larvae incubated at 24 °C and challenged with LPS at 32 °C, limited innate immune response were up-regulated, and additional hypoxia and oxidative processes were observed. Genes annexin A2a, S100 calcium binding protein A10b, and lymphocyte antigen-6, epidermis were identified as promising candidates for LPS recognition and signal transduction.
Low incubation temperature during early development negatively affects survival and related innate immune processes in zebrafish larvae exposed to lipopolysaccharide.
Specimen part, Cell line, Subject
View SamplesLacciac Acid A was indentified as an inhibitor of DMNT1. MCF-7 cells were treated with Lacciac Acid A (200 uM) for 5 days. Changes in gene expression were identified by using Affymetrix Human gene ST1.0 arrays. We used microarrays to determine global changes in gene expression upon treatment with Lacciac Acid A an inhibitor of DMNT1.
Laccaic acid A is a direct, DNA-competitive inhibitor of DNA methyltransferase 1.
Specimen part
View SamplesThe role of Sca-1 on mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression changes in Sca-1 KO mice versus wild-type mice and determine the differential responses to MP and DMBA-induced Mammary carcinogenesis
Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.
Specimen part, Treatment
View Samples