Airway mucus obstruction triggers macrophage activation and MMP12-dependent emphysema
Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.
Specimen part
View SamplesAlveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.
Keratinocyte growth factor and dexamethasone plus elevated cAMP levels synergistically support pluripotent stem cell differentiation into alveolar epithelial type II cells.
Specimen part, Treatment
View SamplesMicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute (Ago) protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. MiRNA expression can be controlled by transcription factors and can therefore be cell type- or tissue-specific. Here we have analyzed miRNA expression profiles in murine monocyte-derived dendritic cells (DCs) and macrophages upon stimulation with LPS, LDL, eLDL and oxLDL to identify not only stimuli-specific miRNA, but also to identify a hierarchical miRNA system involving miR-155. For this, miR-155 knockout dendritic cells and macrophages were also sequenced using the same stimuli. Overall design: Sequencing of murine monocyte-derived dendritic cells and macrophages (each wild type and miR-155 knock out cells) matured and stimulated, respectively, by LPS, oxLDL, eLDL or LDL.
A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation.
Specimen part, Cell line, Subject
View Samplesperipheral blood samples of two leukemia patients in remission were profiled by single cell RNA sequencing approximately 1 year after receiving WT1 specific transgenic T cell therapy, at a time when patients were in clinical remission Overall design: single cell RNA sequencing of peripheral blood mononuclear cells
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Specimen part, Disease, Subject
View SamplesmicroRNAs (miRNAs) are small non-coding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3’ untranslated region (UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer-independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected. Overall design: Examination of miRNAs associated with endogenous human Ago1-4 in HeLa cells
microRNAs associated with the different human Argonaute proteins.
No sample metadata fields
View SamplesExon expression profiling was performed on 37 clinical DLBCL samples and subsequently analyzed using alternative splice analysis of vairance (asANOVA) implemented in Partek Genomics Suite in order to identify alternative spliced genes.
Expression of NOTCH3 exon 16 differentiates Diffuse Large B-cell Lymphoma into molecular subtypes and is associated with prognosis.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
No sample metadata fields
View SamplesThe specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of catenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs.
E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis.
No sample metadata fields
View Samples12-oxo-phytodienoic acid (OPDA) and phytoprostane A1 (PPA1) are cyclopentenone oxylipins that are formed via the enzymatic
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
No sample metadata fields
View SamplesPlant hypocotyls elongate in response to darkness. The response to darkness is gated by the circadian clock, such that wild-type plants (Col) only respond to darkness with growth once every 24 hours, whereas arrhythmic lines, such as CCA1-34, will respond to darkness with growth at any time of day. The experiment here was designed to find genes whose expression was correlated with growth. It should also pick up other genes that are gated by the circadian clock or that are direct targets of CCA1.
Rhythmic growth explained by coincidence between internal and external cues.
Age, Specimen part
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