Characterization of transcriptional heterogeneity and novel therapeutic targets using single cell RNA-sequencing of primary and circulating Ewing sarcoma cells.

Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.

A Confirmation for the Positive Electric Charge of Bio-Molecular Motors through Utilizing a Novel Nano-Technology Approach In Vitro.

Molecular motors are microtubule-based proteins which contribute to many cell functions, such as intracellular transportation and cell division. The details of the nature of the mutual interactions between motors and microtubules still needs to be extensively explored. However, electrostatic interaction is known as one of the key factors making motor-microtubule association possible. The association rate of molecular motors to microtubules is a way to observe and evaluate the charge of the bio-motors in vivo. Growing evidence indicates that microtubules with distinct structural compositions in terms of beta tubulin isotypes carry different charges. Therefore, the electrostatic-driven association rate of motors-microtubules, which is a base for identifying the charge of motors, can be more likely influenced. Here, we present a novel method to experimentally confirm the charge of molecular motors in vitro. The offered nanotechnology-based approach can validate the charge of motors in the absence of any cellular components through the observation and analysis of the changes that biomolecular motors can cause on the dynamic of charged microspheres inside a uniform electric field produced by a microscope slide-based nanocapacitor. This new in vitro experimental method is significant as it minimizes the intracellular factors that may interfere the electric charge that molecular motors carry.