Cell migration is an instrumental process that ensures cells are properly positioned to support the specification of distinct tissue types during development. To provide insight, we used fluorescence activated cell sorting (FACS) to isolate two migrating cell types from the Drosophila embryo: caudal visceral mesoderm (CVM) cells, precursors of longitudinal muscles of the gut, and hemocytes (HCs), the Drosophila equivalent of blood cells. ~350 genes were identified from each of the sorted samples using RNA-seq, and in situ hybridization was used to confirm expression within each cell type or, alternatively, within other interacting, co-sorted cell types. To start, the two gene expression profiling datasets were compared to identify cell migration regulators that are potentially generally-acting. 73 genes were present in both CVM cell and HC gene expression profiles, including the transcription factor zinc finger homeodomain-1 (zfh1). Comparisons with gene expression profiles of Drosophila border cells that migrate during oogenesis had a more limited overlap, with only the genes neyo (neo) and singed (sn) found to be expressed in border cells as well as CVM cells and HCs, respectively. Neo encodes a protein with Zona pellucida domain linked to cell polarity, while sn encodes an actin binding protein. Tissue specific RNAi expression coupled with live in vivo imaging was used to confirm cell-autonomous roles for zfh1 and neo in supporting CVM cell migration, whereas previous studies had demonstrated a role for Sn in supporting HC migration. In addition, comparisons were made to migrating cells from vertebrates. Seven genes were found expressed by chick neural crest cells, CVM cells, and HCs including extracellular matrix (ECM) proteins and proteases. In summary, we show that genes shared in common between CVM cells, HCs, and other migrating cell types can help identify regulators of cell migration. Our analyses show that neo in addition to zfh1 and sn studied previously impact cell migration. This study also suggests that modification of the extracellular milieu may be a fundamental requirement for cells that undergo cell streaming migratory behaviors. Overall design: Examination of genes expressed in two migrating cell populations (CVM and hemocytes) during their active cell migration and the rest of cell types of corresponding stages
Comparative analysis of gene expression profiles for several migrating cell types identifies cell migration regulators.
Specimen part, Subject
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis.
Cell line
View SamplesAPRIL (TNFSF13) is a ligand of the TNF superfamily which binds to two receptors, BCMA and TACI. We have found that APRIL and its receptor BCMA are specifically enhanced in hepatocellular carcinoma, as compared to non-cancerous liver tissue. We further identified that HepG2 cells present the same ligand/receptor pattern as human hepatocellular carcinomas. We investigated the role of APRIL in HepG2 gene expression in a time course study.
APRIL binding to BCMA activates a JNK2-FOXO3-GADD45 pathway and induces a G2/M cell growth arrest in liver cells.
Specimen part, Cell line
View SamplesLung adenocarcinoma (LUAD)-derived oncogenic Wnts increase cancer cell proliferative/stemness potential, but whether they also impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. Wnt1 correlated strongly with tolerogenic genes on the TCGA expression data. In another cohort, Wnt1 was inversely associated with T cell abundance. Altering Wnt1 expression profoundly affected growth of murine lung adenocarcinomas and this was strongly dependent on conventional dendritic cells and T cells. Mechanistically, Wnt1 lead to transcriptional silencing of CC/CXC chemokines in dendritic cells and T cell cross-tolerance. Wnt-target genes were up-regulated in human intratumoral dendritic cells and decreased upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-loaded nanoparticles as single therapy or part of combinatorial immunotherapies acted at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 enhances adaptive immune rejection of lung adenocarcinomas and highlight its potential targeting as a novel therapeutic strategy Overall design: RNAseq data of two DC subsets of 4 patients with lung adenocarcinomas (LUADs).
Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.
Sex, Age, Specimen part, Subject
View SamplesGroup 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens, allergens, tissue remodeling and metabolic homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated but co-receptor mediated negative regulatory axis is yet to be defined.
PD-1 regulates KLRG1<sup>+</sup> group 2 innate lymphoid cells.
Specimen part
View SamplesThis study showed that the oncogenic ligand Wnt1 silences chemokine genes in dendritic cells, leading to impaired cross-priming of T cells in lung adenocarcinoma. Blocking Wnt1 enhanced rejection of tumors by acting concomitantly at the cancer and immune cell level. Overall design: 3' RNA-Seq (QuantSeq) profiling of sorted cDCs populations from WNT1 overexpressing and control (Empty) lung tumors.
Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.
Specimen part, Cell line, Subject
View SamplesTranscriptomic comparison of FVB mouse strain lung Cells one week upon injecting mice intraperitoneally with either saline or Urethane. Mouse lung cell were also compared at the transcriptomic level with the mouse lung adenocarcinoma cell line FULA 1, which was established in our lab
IκB Kinase α Is Required for Development and Progression of <i>KRAS</i>-Mutant Lung Adenocarcinoma.
Specimen part, Cell line, Treatment
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion.
Cell line, Treatment
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
<i>NRAS</i> destines tumor cells to the lungs.
Specimen part, Cell line
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Mutant KRAS promotes malignant pleural effusion formation.
Specimen part, Cell line
View Samples