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Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-cell acute lymphoblastic leukemia patients

ABSTRACT: Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-cell acute lymphoblastic leukemia patients

PROVIDER: PRJNA999346 | ENA |

REPOSITORIES: ENA

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Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-cell acute lymphoblastic leukemia patients

Project description:Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative regulation of the cell cycle, suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. Overall, this signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.

2023-12-03 | GSE239467 | GEO

Identification of extracellular vesicle miRNA cargo

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BAG6KO impacts extracellular vesicle mRNA cargo

Project description:The mRNA cargo of B-16V and B-16V-delta-BAG6 cells was sequenced with RNA seq.

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Comparison of extracellular vesicle miRNA cargo of Adult and Fetal MSCs

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miRNA sequencing detecting miRNA cargo from PRP derived exosomes isolated from young donors and old donors

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Identification of osteolineage cell-derived extracellular vesicle cargo implicated in hematopoietic support

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Project description:Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA (miRNA) and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine.

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Extracellular vesicle cargo change in 3D tumor organoids as compared to conventional 2D glioblastoma cell systems

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Identification of osteolineage cell-derived extracellular vesicle cargo implicated in hematopoietic support

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