Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalance, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31-dependent gene expression was determined in 3-dimensional organotypic skin models.
Control of the Physical and Antimicrobial Skin Barrier by an IL-31-IL-1 Signaling Network.
Sex, Specimen part
View SamplesPrimary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [RNA-seq] Overall design: RNA was isolated from 1,000,000 cells of three MSC donors (59, 64, and 73 years old) at passage 4 and passage 13 using the miRNeasy Mini Kit (Qiagen). Gene expression profiles were analzyed by deep sequencing with IlluminaHiSeq 2000 technology with a read length of 50 bases at EMBL gene core facility (Heidelberg, Germany).
Replicative senescence is associated with nuclear reorganization and with DNA methylation at specific transcription factor binding sites.
No sample metadata fields
View SamplesWe decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Cell line, Subject
View SamplesTissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. Overall design: RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Specification of tissue-resident macrophages during organogenesis.
Specimen part, Subject, Time
View SamplesTissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. Overall design: RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates
Specification of tissue-resident macrophages during organogenesis.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation.
Specimen part, Treatment
View SamplesLong non coding RNAs are implemented in epigenetic changes and regulation of gene expression. HOTAIR is a promising lncRNA concerning epigenetic regulation. We performed HOTAIR overexpression and knockdown experiments in mesenchymal stromal cells derived from bone marrow. After two weeks cells were harvested and RNA and DNA were isolated. Analysis of gene expression was performed with Human Gene 2.0 ST Array (Affymetrix, Santa Clara, USA). Analysis of DNA methylation was performed with Infinium HumanMethylation450 BeadChips (Illumina, San Diego, USA)
The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation.
Specimen part, Treatment
View SamplesDirect conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. Additionally, the single seeded induced NSCs were able to form NSC colonies with efficiency comparable to control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating and attaining neural phenotypes after transplantation into neonatal mouse- and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts. Overall design: RNA-Seq of 3 replicates each of iNSC, WT-NSC, and HNF
Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor.
No sample metadata fields
View SamplesA gene co-expression network analysis has been conducted to identify T2D-associated gene modules. Donors 1-48 were used for the initial analysis and donors 49-80 for the replication and were normalized separately in this study
Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes.
Sex, Age, Specimen part
View SamplesDendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the dendritic cell precursors within the peripheral blood.
Mapping the human DC lineage through the integration of high-dimensional techniques.
Specimen part, Subject
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