Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns.
Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition.
Specimen part
View SamplesThis experiment was specifically designed to measure neural targets of Shh signaling, we sought to profile the genes upregulated by Hh signaling in the ventral neural tube to obtain a valid dataset. To obtain ventral-specific markers, we generated retinoic acid-treated EBs grown in the presence or absence of HH-Ag. We did not observe induction of ventral Hh markers in RA-treated constitutive Gli1FLAG EBs and used these for the control, baseline set. The presence of FoxA2, Nkx2.9 and Nkx6.1 amongst the top 10 genes based on expression levels suggests that profiling significantly enriches for Hh-dependent cell types. As expected, the benchmark standard Gli1 was not up-regulated in our array, since it is constitutively expressed in the control as well.
Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning.
No sample metadata fields
View SamplesOwing to the risk of insertional mutagenesis, viral transduction has been increasingly replaced by nonviral methods to generate induced pluripotent stem (iPS) cells. We report the use of minicircle DNA, a vector type that is free of bacterial DNA and capable of high expression in cells. Here we use a single minicircle vector to generate transgene-free iPSCs from adult human adipose stem cells. (Note: Our Nature Methods publication included analysis of array data from GSM378832 (Foreskin), GSM378833-GSM378838 (JT-iPSC), and GSM378817-GSM378820 (H1, H7, H9, H13, H14) in conjunction with this series).
A nonviral minicircle vector for deriving human iPS cells.
Specimen part
View SamplesNatural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy.
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
Specimen part, Treatment, Time
View SamplesWe report the RNA-seq results from mouse T-cell precursors in different developmental stages including DN1, DN2a, DN2b, DN3 and DP in order to study the gene regulation network in T cell development. Some of the samples also have certain kind of perturbations, such as Bcl11b knockout and the treatment of Notch signaling pathway inhibitor GSI, in order to study the roles of these factors in T cell development. Overall design: Examine the transcriptome of 47 mouse T-cell precursor samples from five developmental stages (DN1, DN2a, DN2b, DN3 and DP). Among them, 19 have Bcl11b knockout and 4 have GSI treatment.
Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network.
Specimen part, Subject
View SamplesDermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined due to a lack of functional subclasses. Here we reveal the presence of multiple lineages of dermal fibroblasts within the dorsal back. Genetic lineage tracing and transplantation assays demonstrate that the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation is carried out by a single, somitic-derived fibroblast lineage. Reciprocal transplantation of distinct fibroblast lineages between the dorsal back and oral cavity induced ectopic dermal architectures that mimic their placeof-origin. These studies demonstrate that intra and inter-site diversity of dermal architectures are set embryonically and maintained postnatally by distinct lineages of fibroblasts. Lineage-specific cell ablation using transgenic-mediated expression of the simian diphtheria toxin receptor in conjunction with localized administration of diphtheria toxin led to diminished connective tissue deposition in wounds and significantly reduced melanoma growth in the dorsal skin of mice. Using flow cytometry and in silico approaches, we identify CD26/DPP4 as a surface marker that allows for the isolation of this fibrogenic, scar-forming lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. The identification and prospective isolation of these lineages holds promise for translational medicine aimed at in vivo modulation of their fibrogenic behavior.
Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.
Specimen part, Treatment
View SamplesHypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sex, Specimen part
View SamplesThe SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Age
View SamplesThe three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Significant and systematic expression differentiation in long-lived yeast strains.
No sample metadata fields
View SamplesWe conducted a genome-wide expression analysis of wild-type males using three cell populations isolated from mitotic, meiotic and post-meiotic phases of spermatogenesis in Drosophila melanogaster. Our approach was to directly isolate testis regions enriched with RNAs from each of the three specific germline phases.
Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes.
Specimen part
View Samples