The side population enriches for leukemia propagating cell activity and Wnt pathway expression in zebrafish acute lymphoblastic leukemia.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA509471 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8312800.fastq.gz | Fastqsanger.gz | |||
| SRR8312801.fastq.gz | Fastqsanger.gz | |||
| SRR8312802.fastq.gz | Fastqsanger.gz | |||
| SRR8312793.fastq.gz | Fastqsanger.gz | |||
| SRR8312803.fastq.gz | Fastqsanger.gz |
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Project description:Cancer stem cells have been strongly linked to resistance and relapse in many malignancies. However, purifying them from within the bulk tumor has been challenging, so their precise genetic and functional characteristics are not well defined. The side population assay exploits the ability of some cells to efflux Hoechst dye via ABC-transporters. Stem cells have increased expression of these transporters and this assay has been shown to enrich for stem cells in various tissues and cancers. This study identifies the side population within a zebrafish model of acute lymphoblastic leukemia and correlates the frequency of side population cells with the frequency of leukemia stem cells (more precisely referred to as leukemia propagating cells within our transplantation model). In addition, the side population within the leukemia evolves with serial transplantation, increasing in tandem with leukemia propagating cell frequency over subsequent generations. Sorted side population cells from these tumors are enriched for leukemia propagating cells and have enhanced engraftment compared to sorted non-side population cells when transplanted into syngeneic recipients. RNA-sequencing analysis of sorted side population cells compared to non-side population cells identified a shared expression profile within the side population and pathway analysis yielded Wnt-signaling as the most overrepresented. Gene set enrichment analysis showed that stem cell differentiation and canonical Wnt-signaling were significantly upregulated in the side population. Overall, these results demonstrate that the side population in zebrafish acute lymphoblastic leukemia significantly enriches for leukemia propagating cells and identifies the Wnt-pathway as a likely genetic driver of leukemia stem cell fate.
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Project description:Cancer stem cells have been strongly linked to resistance and relapse in many malignancies. However, purifying them from within the bulk tumor has been challenging, so their precise genetic and functional characteristics are not well defined. The side population assay exploits the ability of some cells to efflux Hoechst dye via ATP-binding cassette transporters. Stem cells have increased expression of these transporters and this assay has been shown to enrich for stem cells in various tissues and cancers. This study identifies the side population within a zebrafish model of acute lymphoblastic leukemia and correlates the frequency of side population cells with the frequency of leukemia stem cells (more precisely referred to as leukemia-propagating cells within our transplantation model). In addition, the side population within the leukemia evolves with serial transplantation, increasing in tandem with leukemia-propagating cell frequency over subsequent generations. Sorted side population cells from these tumors are enriched for leukemia-propagating cells and have enhanced engraftment compared to sorted non-side population cells when transplanted into syngeneic recipients. RNA-sequencing analysis of sorted side population cells compared to non-side population cells identified a shared expression profile within the side population and pathway analysis yielded Wnt-signaling as the most overrepresented. Gene set enrichment analysis showed that stem cell differentiation and canonical Wnt-signaling were significantly upregulated in the side population. Overall, these results demonstrate that the side population in zebrafish acute lymphoblastic leukemia significantly enriches for leukemia-propagating cells and identifies the Wnt pathway as a likely genetic driver of leukemia stem cell fate.
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Project description:Gene expression profiling of side population cells (SP) and CD146+ cells from primary human osteosarcoma. We aimed to identify genes that differentially regulated between the tumor propagating cells and the bulk tumor cells.
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Project description:Gene expression profiling of side population cells (SP) and CD146+ cells from primary human osteosarcoma. We aimed to identify genes that differentially regulated between the tumor propagating cells and the bulk tumor cells. Total RNA was isolated from SP, Non-SP(NSP), CD146+ and CD146- cells. The RNA is converted to cDNA using Nugen Ovation Kit (Nugen, CA, USA) and subjected to Illumina HT-12 array.
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Project description:Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent vascular structures and endosteal linings in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a novel niche. We investigated patients’ BM biopsies and found evidence of a similar process in patients receiving induction-therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or niche-CPC interaction. We therefore identified a therapy-induced niche that protects CPCs. We used microarrays to compare the gene expression profile of ALL cell line (Nalm-6) from model (A0D) mice and rediduel cells from Ara-C treatment for 2 days (A2D) mice. Engrafted NALM-6-GFP+ cells from A0D mice and residual cells from A2D mice were flow sorted. Total RNA was isolated using RNeasy micro kit (Qiagen). Biotinylated cRNA was hybridized using HGU133Plus 2.0 GeneChip arrays (Affymetrix).
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