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GSE45494
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, -catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees.
Publication Title
Wnt activation in nail epithelium couples nail growth to digit regeneration.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Microarray gene expression experiments to identify differentially expressed genes and pathways in Jag1 conditional/null livers reveal up-regulation of many genes related to fibrosis and ECM interactions.
Publication Title
Microarray data reveal relationship between Jag1 and Ddr1 in mouse liver.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, stochastic segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant decreases in mandibular height and elongated maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Therefore, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders.
Publication Title
Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Ion Torrent Proton
Description
Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions. Overall design: RNA from cultured satellite cells on Ion torrent sequencer
Publication Title
RNA-Seq analysis of isolated satellite cells in Prmt5 deficient mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify genes that are regulated from the lncRNA ANRIL (EXON 13), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
Publication Title
The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.
Publication Title
Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Abstract: Human 6-sulfo LacNac (slan)+ cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DC. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood. Using genome-wide transcriptional profiling as well as extensive functional tests, we clearly show that slan+ cells form a distinct, non-DC-like, population. They cluster away from both DC subsets and their gene expression profile evidently suggests involvement in distinct inflammatory processes. An extensive comparison with existing genomic data sets also strongly confirmed the relationship of slan+ with the monocytic compartment rather than with DC. From a functional perspective, their ability to induce CD4+ and CD8+ T cell proliferation is relatively low. Combined with the finding that antigen presentation by MHC class II is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression of complement receptors on their cell surface, together with their high secretion of IL-1 and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies.
Publication Title
Transcriptional profiling reveals functional dichotomy between human slan<sup>+</sup> non-classical monocytes and myeloid dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 208 Downloadable Samples
- Illumina HiSeq 2500
Description
we report single cell expression profiles of embryonic cells (from day 5 to 11) of pig embryo development. Overall design: single cell transcriptomes were generated from 220 cells obtained from 28 embryos (15 male and 13 female)
Publication Title
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2000
Description
Xist is indispensable for X chromosome inactivation (XCI) in female mammalian cells. However, how Xist RNA directs chromosome-wide transcriptional inactivation of the X chromosome is largely unknown. Here, to study chromosome inactivation by Xist, we generated a system where ectopic Xist expression can be induced from several genomic contexts in aneuploid mouse ES cells. We found that ectopic Xist expression from any location on the X chromosome faithfully recapitulated endogenous XCI, showing the potency of Xist to initiate XCI. Genes that escape XCI remain consistently transcriptionally active upon ectopic XCI, regardless of their position relative to Xist transgenes, and the enrichment of CTCF at their promoters is implicated in directing XCI escape. Xist expression from autosomes facilitates their transcriptional silencing to different degrees, and gene density in proximity of the Xist transcription locus plays a central role in determining the efficiency of gene inactivation. We also show that the enrichment of LINE elements together with a specific chromatin environment facilitates Xist-mediated silencing of both X-linked and autosomal genes. These findings provide new insights into the epigenetic mechanisms that mediate XCI and identify genomic features that promote Xist-mediated chromosome-wide gene inactivation Overall design: 60 RNA-seq from mouse embryonic stem cells and fully differentiated neurons in which ectopic Xist epression is either triggered (plus samples) or not (minus samples) upon doxycycline treatment.
Publication Title
Genetic and epigenetic features direct differential efficiency of Xist-mediated silencing at X-chromosomal and autosomal locations.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Sus scrofa
- 18 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Enterotoxigenic Escherichia coli (ETEC) strains that produce both heat-stable (ST) and heat-labile (LT) enterotoxins cause severe post-weaning diarrhea in piglets. However, the relative importance of the individual enterotoxins to the pathogenesis of ETEC infection is poorly understood. In this study, we investigated the effect on virulence of an F4+ ETEC strain when removing some or all of its enterotoxins. Several isogenic mutant strains were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). Host early immune responses induced by these mutant strains 4h after infection were compared to the wild type strain GIS26 (O149:F4ac+, LT+ STa+ STb+). At the same time, the immune response of this wild type ETEC strain was compared to the mock-infected control, demonstrating the expression of porcine inflammatory response genes. For these purposes, the small intestinal segment perfusion (SISP) technique and microarray analysis were used and results were validated by qRT-PCR. We also measured net fluid absorption of pig small intestinal mucosa 4h after infection with wild type ETEC, the mutant strains and PBS (mock-infected). These data indicate an important role for STb in inducing small intestinal secretion early after infection. The microarray analysis of the different mutant strains also revealed an important role for STb in ETEC-induced immune response by the significant differential regulation of immune mediators like matrix metalloproteinase 3, interleukin 1 and interleukin 17. We conclude that STb can play a prominent role in ETEC-induced secretion and early immune response.
Publication Title
Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples