Although early developmental processes involve cell fate decisions that define the body axes and establish progenitor cell pools, development does not cease once cells are specified. Instead, most cells undergo specific maturation events where changes in the cell transcriptome ensure that the proper gene products are expressed to carry out unique physiological functions. Pancreatic acinar cells mature post-natally to handle an extensive protein synthetic load, establsih organized apical-basal polarity for zymogen granule trafficking, and assemble gap-junctions to perimt efficient cell-cell communication. Despite significant progress in defining transcriptional networks that control initial acinar cell specification and differentiation decisions, little is know regarding the role of transcription factors in the specification and maintenance of maturation events. One candidate maturation effector is MIST1, a secretory cell-restricted transcription factor that has been implicated in controlling regulated exocytosis events in a number of cell types. Embryonic knock-out of MIST1 generates acinar cells that fail to establish an apical-basal organization, fail to properly localize zymogen granule and fail to communicate intra-cellularly, making the exocrine organ highly suceptible to pancreatic diseases.
Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells.
Age, Specimen part
View SamplesHematopoietic stem and progenitor cells (Lineagelo ScaI+ c-Kit+) were sorted 4 weeks post pIpC injection. RNA was extracted using TRIZOL and RNEASY RNA extraction kit. RNA was then amplified using NUGEN Pico amplification kit, fragmented and hybridized on Mouse Expression Array 430 2.0. Signal normalization was performed by RMA method. Data were analyzed using GSEA across the complete list of genes ranked by signal-to-noise ratio.
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs.
Specimen part
View SamplesRNA-seq analysis documented mRNA changes in total pancreatic RNA preparations 6 days after Ptf1a inactivation. Overall design: pancreas mRNA profiles of Tamoxifen treated adult control mice [Ptf1a(CreER/+)] and Ptf1a conditional knockout mice [Ptf1a(CreER/fl)] were generated by deep sequencing using an Illumina Hiseq 2500.
Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and Homeostasis by PTF1A.
Specimen part, Subject
View SamplesRNA-seq analysis of RNA from embryonic day 18.5 pancreas Overall design: pancreas mRNA profiles of E18.5 C57Bl/6 mice were generated by deep sequencing using an Illumina Hiseq 2500.
Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and Homeostasis by PTF1A.
Specimen part, Cell line, Subject
View SamplesLeukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Genetic and epigenetic alterations cause a dysregulated developmental program in leukemia. The MSI2 RNA binding protein has been previously shown to predict poor survival in leukemia. We demonstrate that the conditional deletion of Msi2 results in delayed leukemogenesis, reduced disease burden and a loss of LSC function. Gene expression profiling of the Msi2 ablated LSCs demonstrates a loss of the HSC/LSC and an increase in the differentiation program. The gene signature from the Msi2 deleted LSCs correlates with survival in AML patients. MSI2’s maintains the MLL self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc and Ikzf2. We further demonstrate that shRNA depletion of the MLL target gene Ikzf2 also contributes to MLL leukemia cell survival. Our data provides evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and a rationale for clinically targeting MSI2 in myeloid leukemia. Overall design: RNA-Seq was performed on sorted c-Kit high leukemic cells from 2 Msi2 -/- and 2 Msi2 f/f mice.
Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.
No sample metadata fields
View SamplesComparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of Msi1 in vivo
The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.
Specimen part
View SamplesFTLD-U is the most common pathological correlate of the neurodegenerative dementia frontotemporal dementia
Variations in the progranulin gene affect global gene expression in frontotemporal lobar degeneration.
No sample metadata fields
View Samplesmouse primary BMDCs were stimulated with tlr ligands and gene expression changes were profiled on Affymetrix arrays
Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.
Specimen part
View SamplesTAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (?NLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display a loss of endogenous mouse nuclear TDP-43 as well as dramatic changes in gene expression as measured by microarray. Here, we analyze RNA-sequencing data from the ?NLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice and High Throughput Sequencing of RNA isolated by CrossLinking ImmunoPrecipitation (HITS-CLIP) data of TDP-43’s RNA binding targets to further investigate the dysregulation of gene expression in the ?NLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ?NLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains. Overall design: RNAseq of bigenic (n=4) ?NLS-hTDP-43 and control nontransgenic (n=4) mouse cortex
Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
Age, Specimen part, Time
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