Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Specimen part, Cell line
View Samples56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Overall design: Cell lines were profiled in their baseline, unperturbed state.
Modeling precision treatment of breast cancer.
No sample metadata fields
View SamplesCD133 (Prominin1) is pentaspan transmembrane glycoprotein expressed in several stem cell populations and cancers. Reactivity with an antibody (AC133) to a glycoslyated form of CD133 has been widely used for the enrichment of cells with tumor initiating activity in xenograph transplantation assays. We have found by fluorescence-activated cell sorting that increased AC133 reactivity in human embryonic stem cells, colon cancer and melanoma cells is correlated with increased DNA content and reciprocally, that the least reactive cells are in the G1/G0 portion of the cell cycle. Continued cultivation of cells sorted on the basis of high and low AC133 reactivity results in a normalization of the cell reactivity profiles indicating that cells with low AC133 reactivity can generate highly reactive cells as they resume proliferation. The association of AC133 with actively cycling cells may contribute to the basis for enrichment for tumor initiating activity.
Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines.
No sample metadata fields
View SamplesCells with slow proliferation kinetics that retain the nuclear label over long time periods – the label-retaining cells (LRCs) – represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells. Overall design: Transcriptome comparison of label-retaining biliary epithelial cells and non-label-retaining biliary epithelial cells (cells with GFP expression were compared to the cells without GFP). Illumina HiSeq 2000 was used to analyze 8 RNA samples from 4 mice.
A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver.
Subject
View SamplesThyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown.
Gene signature of the post-Chernobyl papillary thyroid cancer.
No sample metadata fields
View SamplesReactive gliosis is a complex process that involves profound changes in gene expression. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of reactive gliosis in optic nerve head in response to optic nerve crush injury.
The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve.
Sex, Specimen part
View SamplesReactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape.
Reversible reactivity by optic nerve astrocytes.
Sex
View SamplesComparison of CLL and MCL primary cells obtained from a patient with MCL variant Richter syndrome
Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years.
Specimen part, Disease, Disease stage
View SamplesIn birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity.
Transcriptomic landscape of the primitive streak.
Specimen part
View SamplesBlood was extracted from embryonic hearts at E4 and E6 and non-red blood was separated by density gradient centrifugation
Expression profiling of circulating non-red blood cells in embryonic blood.
No sample metadata fields
View Samples