Langerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. In contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, we found that oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103+CD11blow (CD103+LCs) and CD11b+CD103- (CD11b+LCs) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103+LCs originate from pre-DCs, whereas CD11b+LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with their epithelial position, morphology and expression of LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DCs and monocytic) in steady state Overall design: The following cells were isolated from mice (2-4 replicates): Lung DCs, mucosal CD103+ LC, mucosal CD11b+ LC, Skin LC. Transcriptome analysis was performed.
Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes.
No sample metadata fields
View SamplesUnder conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor 1 apoprotein.
During hormone depletion or tamoxifen treatment of breast cancer cells the estrogen receptor apoprotein supports cell cycling through the retinoic acid receptor α1 apoprotein.
Cell line
View SamplesIn embryonic stem cells (ESCs), the expression of development-related genes, including germ cellrelated genes, is globally repressed. The transcription factor MAX represses germ cellrelated gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cellrelated gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cellrelated gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cellrelated genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cellrelated genes in ESCs.
DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells.
Specimen part, Cell line
View SamplesHuntingtons disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntingtons disease and wild type iPSCs derived GABA MS-like neurons has been performed.
Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.
Age, Specimen part
View SamplesNeural precursor cells (NPCs) in the mammalian neocortex generate various neuronal and glial cell types in a developmental stage-dependent manner. Most neocortical NPCs lose their neurogenic potential after birth. We have previously shown that high mobility group A (HMGA) proteins confer the neurogenic potential on early-stage NPCs during the midgestation period, although the underlying mechanisms are not fully understood. Here we performed microarray analysis and compared expression profiles between control and HMGA2-overexpressed NPCs.
IMP2 regulates differentiation potentials of mouse neocortical neural precursor cells.
Specimen part
View SamplesRed light can affect a variety of responses in Arabidopsis. We characterize the early gene expression patterns of seedlings exposed to 1 hour of red light using a small sized sample of 5, 7-day-old seedlings and also performed dark controls.
Extraction and labeling methods for microarrays using small amounts of plant tissue.
No sample metadata fields
View SamplesPurpose: The ability of adult zebrafish tissues to undergo dedifferentiation provides an opportunity to probe the molecular underpinnings of cell identity and reprogramming. Zebafish muscle regeneration utilizes dedifferentiation to reprogram mature multinucleated myocytes into dedifferentiated myoblast that re-enter the cell cycle. A unique advantage of this system is that the regenerating cell mass is large and fairly homogenous, facilitating genomics approaches to uncovering the underlying biology. Methods: To better understand cellular reprogramming of mature myocytes, we temporally analyzed the changing transcriptome leading up to the proliferative switch. RNA was obtained after Laser Micro-dissection (LMD) of Control, 9 hour post-injury (HPI) or 18 HPI using Trizol and micro column purification. Illumina''s TruSeq Stranded mRNA Library Prep Kit and 0.1 - 4 µg total mRNA from pooled purified RNA samples were used for performing ribosomal-depletion (Ribo-Zero Gold rRNA Removal Kit, Illumina) and library preparation. Sequencing was performed by the UM DNA Sequencing Core, using an Illumina Hi-Seq 2000 (50-cycle, single end read) platform. Results: Clustering and functional annotation of differentially expressed genes highlighted the importance of catabolic and phagocytic processes upregulation at 9 and 18 hours post injury (hpi). Furthermore, genes encoding principle regulators of chromatin states were actively re-regulated during the reprogramming process. Utilizing the accessibility of these tissues in the zebrafish model, kKnockdown experiments enabled in vivo validation and phenotypic analysis of candidate genes and pathways for their roles in genomic and cellular reprogramming. Additionally, we found that despite of their low expression levels, lncRNAs were highly represented in gene clusters with dynamic, “switch-like” expression profiles, and that miRNA processing was also found important for reprogramming Conclusions: We conclude that reprogramming of a “post-mitotic” myocyte into a dedifferentiated myoblast requires both heritable yet nuanced epigenetic alterations and molecular switches that involve transcription factors, miRNA and lncRNA, while maintaining the lineage restriction of the cell of origin. Overall design: Early time points post injury (9 & 18 hours) mRNA and lncRNA profiles of Zebrafish lateral eye muscle (EOM) were generated by deep sequencing, in quadruplicate, using Illumina Hi-seq.
Temporally distinct transcriptional regulation of myocyte dedifferentiation and Myofiber growth during muscle regeneration.
No sample metadata fields
View SamplesMutations of the transcriptional regulator Mecp2 cause the X-linked autism spectrum disorder Rett syndrome (RTT), and Mecp2 has been implicated in several other neurodevelopmental disorders. To identify potential target genes regulated directly or indirectly by MeCP2, we performed comparative gene expression analysis via oligonucleotide microarrays on Mecp2-/y (Mecp2-null) and wild-type CPN purified via fluorescence-activated cell sorting (FACS).
Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice.
Specimen part
View SamplesThese investigations studied the fundamentals of how plants perceive gravity and develop in microgravity. It informs how gene regulation is altered by spaceflight conditions.
Comparative transcriptomics indicate changes in cell wall organization and stress response in seedlings during spaceflight.
Specimen part
View SamplesThe recently proposed exozyme hypothesis posits that subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic test of this hypothesis, we examine the role of Dis3 -- an essential polypeptide with endo- and 3'' to 5'' exo-ribonuclease activity -- in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutation: (i) accumulate anaphase and pre-anaphase mitotic spindles; (ii) exhibit spindles that are mis-oriented and displaced from the bud neck; (iii) harbor elongated spindle-associated astral MTs; (iv) have an increased G1 astral MT length and number; and (v) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4 -- but not other exosome subunit gene mutants -- also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and microtubule-related transcripts in mutant strains. Collectively, the different mitotic phenotypes and distinct sets of mRNAs affected by the exosome subunit and cofactor mutants studied here suggest that Dis3 has a core exosome-independent role(s) in cell cycle progression. These observations are consistent with the predictions of the exozyme hypothesis and also suggest an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs, and mitotic progression. Overall design: RNA-seq analysis of total RNA harvested from WT, mtr3-1, mtr4-1, and Dis3^mtr (rrp44-1/mtr17-1) Saccharomyces cerevisiae strains after a temperature shift.
Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant.
Cell line, Treatment, Subject
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