Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers. Overall design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.
Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.
Cell line, Subject
View SamplesHair follicle matrix, outer root sheath, dermal papilla cells and melanocytes and a dermal fraction enriched in fibroblasts were FACS isolated from 4d backskins. Targets from two biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Genechip 430A arrays. Comparisons between the sample groups allow the identification of cell-type specific genes.
Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.
No sample metadata fields
View Samples2H2O has a long history as a protein or amino acid labeling techinique, and such labeling systems have proven effective for many different types of studies. A disadvantage of a 2H2O labeling system is that plant growth is inhibited as the percentage of deuterium in the medium increases. However the molecular effects of 2H2O on plant growth has not previoulsly been investigated.
Measuring the turnover rates of Arabidopsis proteins using deuterium oxide: an auxin signaling case study.
Specimen part
View SamplesThe aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children.
Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention.
Sex, Age, Specimen part, Treatment
View SamplesHair Follicle regeneration relies on both epithelial components (bulge and hair germ cells) and a mesenchymal one (dermal papilla cells).
A two-step mechanism for stem cell activation during hair regeneration.
Specimen part
View SamplesDifferential expression of Hdc-GFPhi HSPC VS Hdc-GFPlo HSPC hematopoetic stem and progenitor cells from mouse bone marrow Overall design: Bone marrow Hdc-GFPhi and Hdc-GFPlo HSPC (LSK, Lin-c-kit+Sca-1+) hematopoetic stem and progenitor cells were isolated from femur, tibia, illium, and vertebra bones of histidine decarboxylase (Hdc) green fluorescent protein (Hdc-GFP) mice Hdc-GFPhi HSPC and Hdc-GFPlo HSPC cells were sorted by combinations of GFP and the cell surface markers of LSK, total RNA was isolated from sorted 2,000 HSPCs using ARCTURUS PicoPure RNA isolation kit (Life Technologies). cDNA was amplified and libraries were constructed by using the SMARTer Ultra Low Input RNA kit (Clontech Laboratories) and the Nextera XT DNA Library Preparation kit (Illumina) according to the respective manufacturer's instructions. Sequencing was performed on the Illumina HiSeq 2500 platform. a. Hdc-GFPhi bone marrow HSPC cells (n=4) b. Hdc-GFPlo bone marrow HSPC cells (n=4)
Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop.
Specimen part, Cell line, Subject
View SamplesIdentification of the role of retinoic acid on the activation of the dHSCs
Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy.
Specimen part
View SamplesThe hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for activating SCs during the adult hair cycle, but the signal exchange between niche and SC precursors/transit amplifying progenitor cells (TACs) that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs and the DP niche express a plethora of known and novel ligands and receptors. Signaling interaction network analysis reveals a birds-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth. Overall design: FACS was used to isolate specific cell types from P5 mouse back skin
Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.
Specimen part, Subject
View SamplesWe co-isolated hair follicle placode and dermal condensate cells along with other specific cell types from E14.5 embryonic mouse skin. With next-generation RNA-sequencing we defined gene expression patterns in the context of the entire embryonic skin. Overall design: FACS was used to isolate specific cell types from E14.5 embryonic mouse skin.
An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin.
No sample metadata fields
View SamplesCpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC
Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.
No sample metadata fields
View Samples