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

Alternate Titles(s): Flura-seq identifies organ-specific adaptations in metastasis-initiating cells

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
Data Type
Equipment Used
Illumina HiSeq 2000
Dataset Format(s)
CSV, SRA
Dataset Size
1.53 MB (CSV), 87.3 GB (SRA)
Data Catalog Record Updated
2021-10-28