We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment.
Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-β and integrin/focal adhesion kinase (FAK) signaling.
Specimen part
View SamplesHair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. We uncovered a hitherto unrecognized DP transmitter, TGF2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration.
Paracrine TGF-β signaling counterbalances BMP-mediated repression in hair follicle stem cell activation.
Sex, Specimen part
View SamplesWe report downstream gene expression changes in stem cells of the adult mouse hair follicle upon conditional ablating of the transcription factor Forkhead Box C1 transcription factor (FOXC1). Hair follicles undergo cycles of rest (telogen; Tel) and regeneration (anagen; Ana). As such, we performed our analysis on these two different stages of hair follicles. Overall design: mRNA-sequencing of WT vs. Foxc1-conditional or inducible KO (Foxc1-cKO or iKO) hair follicle stem cells (HFSCs) purified from mouse dorsal back skin by flow-activated cell sorting (FACS).
FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.
Specimen part, 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 SamplesCanonical WNT-signaling is essential for placode formation irrespective of appendage type. At sites of placode initiation, Although WNT-signaling occurs in both epithelium and mesenchyme, the site of most intense activity as revealed by the WNT reporter Axin2-LacZ was in a zone just below the epithelial-mesenchymal interface. In ventral foot-skin, this WNT activity peaked at E17.5, concomitant with sweat bud fate commitment, while in dorsal back-skin, it began at E14.5, concomitant with HF fate specification. Overall design: To address whether WNT-signaling within this zone might regionally influence the transcriptional landscape of body-site mesenchymes to support distinct epithelial fates, we transcriptionally profiled the Axin2-positive and Axin2-negative dermal cells following their FACS-purification from E17.5 ventral foot-skin and E14.5 dorsal back-skin
Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.
Specimen part, Subject
View SamplesWe performed RNA-seq on purified squamous cell carcinoma stem cells (SCC-SCs) from primary mouse skin tumors transduced with TGF-beta reporter. Overall design: SCC-SCs were purified based on cell surface marker expression integrin alpha6 and CD44, after lineage negative selection, and separated by fluorescent TGF-beta reporter expression.
TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesDuring development, a polarized sheet of epidermal cells undergoes stratification and differentiation to produce the skin barrier. Through mechanisms poorly understood, the process involves adhesion and Notch signaling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted transcription factor serum response factor (SRF), which has been shown to be essential for proper epidermal differentiation in vitro and in vivo. Seeking mechanism, we identified actomyosin-related genes as well-known SRF targets downregulated shortly after ablation. We show that this results in a diminished cortical actomyosin network which fails to regulate the transition of cells from the basal proliferative layer to the suprabasal differentiating layer resulting in an inability of cells to properly execute stratification and differentiation.
Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
No sample metadata fields
View SamplesIncreasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesHIV-1 and HIV-2 can both infect humans, but HIV-2 causes a slow progressing disease and is well controlled by the immune system for prolonged period of times.
HIV-1 and HIV-2 differentially mature plasmacytoid dendritic cells into IFN-producing cells or APCs.
Treatment, Subject, Time
View Samples