Neuronal migration disorders such as lissencephaly and subcortical band heterotopia (SBH) are associated with epilepsy and intellectual disability. Doublecortin (DCX), LIS1 and alpha1-tubulin (TUBA1A), are mutated in these disorders, however corresponding mouse mutants do not show heterotopic neurons in the neocortex. On the other hand, the spontaneously arisen HeCo mouse mutant displays this phenotype. The study of this model reveals novel mechanisms of heterotopia formation. While, HeCo neurons migrate at the same speed as WT, abnormally distributed dividing progenitors were found throughout the cortical wall from E13. Through genetic studies we identified Eml1 as the mutant gene in HeCo mice. No full length transcripts of Eml1 were identified due to a retrotransposon insertion in an intron. Re-expression of Eml1, coding for a microtubule-associated protein, rescues the HeCo progenitor phenotype. We further show that EML1 is mutated in giant ribbon-like heterotopia in human. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human.
Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.
Specimen part
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WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.
Cell line
View SamplesA highly metastatic breast cancer cell line, 4T1, was used to generate stable Wnt5a expressing and vector only control cells. Cells were generated using lentivirus infection and selection with blasticidin. Expression of Wnt5a was confirmed using western blot. Cell behaviour was characterized. Wnt5a expressing cells exhibited reduced migration in a transwell assay and reduced metastasis in a tail vein injection assay. Growth was not significantly affected.
WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.
Cell line
View SamplesTo investigate differential gene expression that might account for the differing glomerular phenotype of NPHS2-Cre +/+ mice when compared with wild-type control, including altered GBM thickness, loss of normal foot process morphology, and decrease in podocyte number, RNA sequencing analysis was performed on glomeruli extracted from both NPHS2-Cre +/+ and wild-type control mice. Overall design: Following isolation of glomeruli using Dynabeads from NPHS2-Cre +/+ and wild-type control mice (n=2 biological replicates per genotype, singly isolated), total RNA was extracted and RNA samples were submited for sample preparation and sequencing.
Podocyte-specific expression of Cre recombinase promotes glomerular basement membrane thickening.
Sex, Age, Specimen part, Cell line, Subject
View SamplesIt is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, It is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming, and show that mitosis may be a driving force of reprogramming. Overall design: Human BJ cells transduced with lentiviral particles of the conventional reprogramming factors (OCT3/4, SOX2 and KLF4) were used as controls. Two types of controls were used: 1) BJ transduced with OSK (OCT4, SOX2 and KFL4) viruses; 2) BJ cells transduced with OSK plus GFP viruses. Experimental treatment was BJ cells transduced with OSK plus BRD3R viruses. RNA was extracted from cells at day 3 of reprogramming because the reprogramming cells are still homogeneous and transgenes are well expressed at this time point.
The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis.
No sample metadata fields
View SamplesKATP opposes depolarization of cells in the heart, smooth muscle, and other tissues by permitting the efflux of potassium ions and this efflux is evidently required to prevent unopposed vasoconstriction and insufficiency of coronary artery blood flow triggered by one or more cytokines induced in response to LPS. The cytokine(s) involved must elicit a dysfunctional response in the Kir6.1-deficient environment, and to gain further insight into the effects of the mutation, we examined the transcriptional status of whole heart, isolated from normal C57BL/6J mice or KcnJ8Md/Md mice, before and after injection of 1 g of LPS
ATP-sensitive potassium channels mediate survival during infection in mammals and insects.
No sample metadata fields
View SamplesRad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21.
Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved.
Specimen part, Time
View SamplesIn addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid -oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated -oxidation-fueled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homolog of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses.
Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production.
Specimen part, Treatment
View SamplesWe report a simultaneous comparison of striatal mRNA levels by RNA sequencing mice with graded levels of HD-like abnormalities Overall design: Examination of 4 different mouse lines
Allelic series of Huntington's disease knock-in mice reveals expression discorrelates.
Specimen part, Subject
View SamplesWe report a transcriptional response in human OECs that encompasses multiple innate immune networks not previously associated with these cells. Major pathways included immune cell trafficking, and differential cytokine production Overall design: We used RNA-based sequencing technology for high-throughput profiling of innate immune responses in human OECs and the role of Burkholderia in triggering these responses
Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells.
No sample metadata fields
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