Project description:NCI-60 cancer cell lines were profiled with their genome-wide gene expression patterns using Affymetrix HG-U133A chips. Keywords: NCI-60 cancer cell line expression profiling
Project description:Generation of research quality, clinically relevant cell types in vitro from human pluripotent stem cells (hPSCs) requires detailed understanding of the equivalent cell types in humans. Here we analyzed 130 human fetal samples at 6-20 weeks of development and identified the stages in which human cKIT+ primordial germ cells (PGCs), the precursors of gametes, undergo whole genome epigenetic reprogramming and ultimately initiation of imprint erasure with loss of both 5mC and 5-hydroxy-mC at differentially methylated regions. Using five alternate in vitro differentiation strategies combined with a single-cell microfluidic analysis, high throughput RNA sequencing and a bona fide human cKIT+ PGC signature, we show that hPSC differentiation generates a rare cKIT+ PGC subtype found in both the human fetal gonad and mouse embryo. Taken together, our study creates a resource of human germ line ontogeny that is absolutely essential for future studies aimed at interpreting in vitro differentiation of the human germ line. cKIT+ cells analyzed from 2 biological samples for testes and 2 samples for ovaries at 16 and 16.5 weeks. 3 biological replicates of TRA-1-60+ cells sorted from H1 hESCs
Project description:Channel catfish (Ictalurus punctatus) and tra catfish (Pangasianodon hypophthalmus) both belong to the order Siluriformes. Channel catfish does not possess an air-breathing organ (ABO), and thus cannot breathe in the air, while tra catfish is a facultative air-breather and use the swim bladder as its air-breathing organ, which provides for aerial breathing in low oxygen conditions. Tra and channel catfish serve as a great comparative model for studying the transition of life from water to terrestrial living, as well as for understanding genes that are crucial for development of the swim bladder and the function of air-breathing in tra catfish. We selected seven developmental stages in tra catfish for RNA-Seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated in tra catfish, and a total of 21, 448 unique genes were detected. A comparative genomic analysis was conducted between channel catfish and tra catfish. Gene expression analysis was performed for these tra catfish specific genes. Hypoxia challenge and microtomy experiments collectively suggested that there are critical timepoints for the development of the air-breathing function and swim bladder development stages in tra catfish. Key genes were identified to be the best candidates of genes related to the air-breathing ability in tra catfish. This study provides a large data resource for functional genomic studies in air-breathing function in tra catfish, and sheds light on the adaption of aquatic organisms to the terrestrial environment.
Project description:The goal of this study is to identify and characterize sites in the C. elegans genome bound by the transcription factor TRA-1. TRA-1 ChIP-seq was performed in the following stages of animals in duplicate: 1) L2 stage of C. elegans wild-type N2 strain; 2) L3 stage of C. elegans wild-type N2 strain; 3) young adult stage of C. elegans glp-4(bn2) mutant; 4) young adult stage of C. elegans spe-11(hc77) mutant; 5) L3 stage of C. briggsae wild-type AF16 strain. As a negative control, TRA-1 ChIP-seq was also performed in C. elegans L3 stage with tra-1(e1834) homozygous and heterozygous mutation. Input DNA was also sequenced in each condition.
Project description:Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1-60 and TRA-1-81, two 'stemness' cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1-60+/TRA-1-81+ cells are chemoresistant compared to TRA-1-60-/TRA-1-81- cells. Transcriptome profiling identified UGT1A10, shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10, eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway.