Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model.
Helio PaisKatia RuggeroJing ZhangOsama Al-AssarNicolas BéryRavneet BhullerVictoria WestonPamela R KearnsCristina MecucciAmi MillerTerence Howard RabbittsPublished in: Scientific reports (2019)
The surfaceome is critical because surface proteins provide a gateway for internal signals and transfer of molecules into cells, and surfaceome differences can influence therapy response. We have used a surfaceome analysis method, based on comparing RNA-seq data between normal and abnormal cells (Surfaceome DataBase Mining or Surfaceome DBM), to identify sets of upregulated cell surface protein mRNAs in an LMO2-mediated T-ALL mouse model and corroborated by protein detection using antibodies. In this model the leukemia initiating cells (LICs) comprise pre-leukaemic, differentiation inhibited thymocytes allowing us to provide a profile of the LIC surfaceome in which GPR56, CD53 and CD59a are co-expressed with CD25. Implementation of cell surface interaction assays demonstrates fluid interaction of surface proteins and CD25 is only internalized when co-localized with other proteins. The Surfaceome DBM approach to analyse cancer cell surfaceomes is a way to find targetable surface biomarkers for clinical conditions where RNA-seq data from normal and abnormal cell are available.
Keyphrases
- rna seq
- single cell
- cell surface
- induced apoptosis
- cell cycle arrest
- high throughput
- mouse model
- primary care
- bone marrow
- healthcare
- emergency department
- cell death
- mesenchymal stem cells
- big data
- signaling pathway
- amino acid
- quality improvement
- machine learning
- small molecule
- binding protein
- artificial intelligence
- replacement therapy
- label free
- real time pcr