Heterozygous and homozygous Pax2 E11.5 embryos were collected and the intermediate mesoderm was dissected and dispersed into single cells.
Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms.
Specimen part
View SamplesLiver RNA was collected from three genotypes: WT controls, KCP knockout (KCP-KO) mutants, and KCP-Transgenic (KCP-Tg) overexpressing mice.
The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice.
Specimen part
View SamplesGlomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.
Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.
Specimen part
View SamplesMethylation of histone H3 lysine 4 (H3K4me) at actively expressed, cell type-specific genes is established during development by the Trithorax group of epigenetic regulators. In mammals, the Trithorax family includes KMT2A-D (MLL1-4), a family of SET domain proteins that function in large complexes to impart mono-, di-, and trimethylation at H3K4. Individual KMT2s and their co-factors are essential for embryonic development and the establishment of correct gene expression patterns, presumably by demarcating the active and accessible regions of the genome in a cell specific and heritable manner. Despite the importance of H3K4me marks in development, little is known about the importance of histone methylation in maintaining gene expression patterns in fully differentiated and non-dividing cell types. In this report, we utilized an inducible cardiac-specific Cre driver to delete the PTIP protein, a key component of a H3K4me complex, and ask whether this activity is still required to maintain the phenotype of terminally differentiated cardiomyocytes. Our results demonstrate that reducing the H3K4me3 marks is sufficient to alter gene expression patterns and significantly augment systolic heart function. These results clearly show that maintenance of H3K4me3 marks is necessary for the stability of the transcriptional program in differentiated cells. The array we performed allowed us to identify genes that are regulated by PTIP and histone methylation.
Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes.
Sex, Specimen part
View SamplesAberrant expression of homeobox transcription factor HOXA9 is a central component of the leukemogenic program driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid progenitor cells and pro-B cells leads to significant rearrangement of the epigenetic landscape with prominent emergence of cancer specific de novo enhancers. HOXA9 acts as a pioneer factor at the de novo enhancers and is required for recruitment of transcription factor CEBP/a and the histone H3K4 methyltransferase MLL3/MLL4 complex. HOXA9 function at the de novo enhancer is distinct from its physiological role at distal enhancers during normal hematopoietic development. Genetic deletion of MLL3/4 specifically affects the active enhancer signatures at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis. Our study reveals a previously uncharacterized role of HOXA9 and the MLL3/4 complex in leukemogenesis and provide mechanistic insights in epigenetic deregulation during malignant transformation. Overall design: RNA-seq for untransformed myeloid progenitors (MP)
HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis.
Specimen part, Cell line, Subject
View SamplesSperm cells of seed plants have lost their motility and are transported by the vegetative pollen tube cell for fertilization. The extent to which sperm cells regulate their own transportation is a long-standing debate. By using the novel Arabidopsis double mutant drop1 drop2, we demonstrate here that sperm cells are only passive cargo and that the vegetative tube cell as a vehicle controls the entire journey. Overall design: the semi-in-vivo pollen tubes of wild type (WT) and drop mutant using single-cell RNA sequencing
Sperm cells are passive cargo of the pollen tube in plant fertilization.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
Specimen part
View SamplesSkin samples from mice in a model of vitiligo were selected for gene expression profiling in order to identify active inflammatory pathways.
CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
Specimen part
View SamplesHuman skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.
Specimen part, Disease, Disease stage
View SamplesGene expression profiles of peripheral blood samples from C57BL/6 mice exposed with ionizing radiation.
Biological pathway selection through Bayesian integrative modeling.
Sex, Specimen part, Treatment, Time
View Samples