Organ-specific in situ transcriptomics of MDA231 cells identified by Flura-seq

UID: 10436

Author(s): Basnet, Harihar*, Tian, Lin*, Massagué, Joan* * MSK affiliated

Description: Summary from the GEO: "Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with unprecedented sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, covalently labeling nascent RNA for purification and sequencing. Flura-seq revealed that breast cancer micrometastases in lung and brain exhibit unique, reversible gene signatures depending on the microenvironment. Specifically, the mitochondrial electron transport Complex I and the NRF2-driven antioxidant programs were induced in oxygen-rich pulmonary micrometastases, compared to mammary tumors or brain micrometastases. Loss of Complex I activity, and antioxidant supplementation potentiated pulmonary metastatic growth. We confirm lung metastasis-specific NRF2 overexpression in clinical samples, thus validating Flura-seq’s utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research."

"Overall design: Examination of 5-FU labeled RNAs in cancer cells present in different organs."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

CNS/Brain
Breast
Lung

Access via GEO
RNA sequence data
Accession #: GSE118937

Access via SRA
RNA Sequence reads for 27 samples
Accession #: SRP158622

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA487361
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus database provides open access to these files. SRA and/or tar files can be downloaded directly from the site or viewed in the NCBI SRA Run Selector (link at bottom of page).
Associated Publications: Basnet H, Tian L, Ganesh K, et al. Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization. eLife. 2019; 8:e43627.
Data Type: Genomic
Equipment Used: Illumina HiSeq 2000
High throughput gene sequencing system
Dataset Format(s): CSV, SRA
Dataset Size: 1.53 MB (CSV), 87.3 GB (SRA)

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