Project description:RNA-sequencing of flow-sorted Smad4 wild-type (WT) or Smad4 knockout (KO) KvPC (i.e. KRASG12V; p53 mutant) pancreatic ductal adenocarcinoma (PDAC) organoids from monocultures or co-cultures with pancreatic stellate cells (PSCs) and RNA-sequencing of flow-sorted PSCs from the same co-cultures. We investigated changes in transcriptome in Smad4 KO KvPC PDAC organoids compared to Smad4 WT KvPC PDAC organoids in monoculture or in co-culture with PSCs. We also investigated the changes in transcriptome in PSCs co-cultured with Smad4 WT or Smad4 KO KvPC PDAC organoids.
Project description:RNA-sequencing of flow-sorted Smad4 wild-type (WT) or Smad4 knockout (KO) KPC (i.e. KRASG12D; p53 mutant) pancreatic ductal adenocarcinoma (PDAC) organoids from monocultures or co-cultures with pancreatic stellate cells (PSCs) and RNA-sequencing of flow-sorted PSCs from the same co-cultures. We investigated changes in transcriptome in Smad4 KO KPC PDAC organoids compared to Smad4 WT KPC PDAC organoids in monoculture or in co-culture with PSCs. We also investigated the changes in transcriptome in PSCs co-cultured with Smad4 WT or Smad4 KO KPC PDAC organoids.
Project description:Lipids play an important role in energy storage, membrane structure stabilization and signaling. Parasitoids are excellent models to study lipidomics because a majority of them do not accumulate during their free-living life-stage. Studies on parasitoids have mostly focused on the changes in the lipids and gene transcripts in hosts and little attention has been devoted to lipidomics and transcriptomics changes in parasitoids. In this study, a relative quantitative analysis of lipids and their gene transcripts in 3-days-old Lysiphlebia japonica larva (3 days after spawning) and pupae were performed using liquid chromatography, mass spectrometry and RNA-seq. Thirty-three glycerolipids and 250 glycerophospholipids were identified in this study; all triglycerides and the vast majority of phospholipids accumulated in the pupal stage. This was accompanied by differentially regulated lipid uptake and remolding. Furthermore, our data showed that gene transcription was up-regulated in key nutrient metabolic pathways involved in lipid synthesis in 3-days-old larvae. Finally, our data suggests that larva and pupa of L. japonica may lack the ability for fatty acids synthesis. A comprehensive, quantitative, and expandable resource was provided for further studies of metabolic regulation and molecular mechanisms underlying parasitic response to hosts defense.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using an unbiased analysis of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in vivo. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.