Project description:To identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression. We established sox11-expressing mouse glioma-initiating cell (GIC)-like cell line (NSCL61s), NSCL61s-sox11, which lost tumorigenicity when transplanted in vivo. We think that genes, which are differently expressed between NSCL61s and NSCL61s-sox11, would be new targets for glioma therapy.
Project description:To identify a novel miRNA that is aberrantly expressed in GICs, we analyzed differences in miRNA expression between the mouse GICs, NSCL61 and OPCL61, showing characteristic features of cancer stem cell, and their parental cells by miRNA microarrays. neural stem cells, glioma-initiating cells (GICs) from neural stem cells, oligodendrocyte precursor cells, glioma-initiating cells (GICs) from oligodendrocyte precursor cells.
Project description:Acute myeloid leukemia (AML) is a hematological malignancy, associated with unfavorable patient outcome primarily due to disease relapse. Since specific early leukemic hematopoietic stem and progenitor cells (HSPCs) are suggested to be responsible for AML propagation, the present study used single cell analysis (SCA) to detect and explore rare relapse-initiating HSPC clones, appearing already at diagnosis. To address inherent SCA limitations, we developed a unique high-resolution technique capable to follow single cell-derived subclones of heterogeneous HSPC subpopulations during AML evolution. Each of these subclones was evaluated for chemo-resistance, in-vivo leukemogenic potential, mutational profile, and the subclone cell of origin identified using reconstruction of phylogenetic trees. This study, employing combined functional and genomic analyses, unraveled the patient-specific HSPC subpopulations involved in chemo-resistance and determined, at time of diagnosis, the phenotype of the relapse-initiating clone, allowing early prediction of AML recurrence and suggesting novel precise therapeutic targets for relapse prevention.
Project description:Neuroblastoma is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. While its exact origin is still under debate, it is assumed to arise from the multipotent neural crest. To understand the origin and clonal development of various neuroblastoma cell states, we analyzed human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Tumor subclones showed considerable inter- individual variation in terms of copy number profiles and transcriptional phenotype. Despite this heterogeneity, transcriptional plasticity between subclones converges on cellular processes related to axon guidance via the SLIT/ROBO pathway, proliferation, and differentiation. Genomic heterogeneity was also observed for MYCN. Subclones harboring 2p/MYCN gain (< 8 copies) co-exist with amplified subclones (> 20 copies), indicating that MYCN amplification may represent a non-initiating genomic event. Beyond adrenergic heterogeneity, we identify a subpopulation of abnormal cells resembling multipotent Schwann cell precursors, characterized by expression programs of proliferation, apoptosis, and a non- immunomodulatory phenotype. Their genomic profile and phylogeny suggest an ancestral, pre-malignant role in tumorigenesis. While the function of these SCP-like cells in tumor initiation remains to be established, their identification expands the reservoir of tumor cells, considering their multipotency reflecting a central neuroblastoma feature.
Project description:Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees. Subclones 2, 3, 6 and 28 produce significantly larger amount of thermogenic activity than the subclones 18, 19, 23 and 24. We compared gene expression profiles of these subclones to identify secreted factors enriched in the more thermogenic clones.