CAtS · Deciphering the developmental roots of childhood sarcoma cells – combining single cell sequencing technologies and machine learning
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-11-09 → 2022-11-08
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Deciphering the developmental roots of childhood sarcoma cells – combining single cell sequencing technologies and machine learning
In Europe, the leading cause of death by disease for children is cancer. For survivors, they live with treatment-related complications for the remainder of their lives highlighting a need for less toxic therapeutic strategies. The CAtS Action, “Cell Atlas of Sarcoma: Deciphering the developmental roots of childhood sarcoma cells” sought to understand how childhood sarcomas develop with the long-term goals of developing new treatment avenues for patients. Sarcomas are cancers of the bone and soft tissue that arise more commonly in children than adults. Sarcomas can develop in almost any part of the body, including the legs, arms and abdomen. Adult cancers arise from the accumulation of mutations over decades each time a cell divides. However, in childhood cancer, the causes of cancer are not understood as clearly. The overall aim of the action was to create a cell ‘atlas’ of sarcoma to find new treatment targets for paediatric patients. We applied single-cell RNA sequencing, a methodology that profiles individual cancer cells within each sample. These profiles can be used to learn what it means to be a sarcoma and how these cells differ from healthy cells. By creating an atlas of sarcoma, we could identify every component of a tumour, with fine resolution, allowing us to determine the differences between healthy and cancer cells and find potential treatment targets. Upon successful completion of this action, we were able to identify foetal genes that were repurposed by cancer cells. These genes should not exist after birth, yet they persist in tumours and contribute to oncogenic progression. Due to the exclusive nature of these genes in these cancers, they are attractive targets for treatment and offer immense translation applications of the atlases we created. The specific objectives of the Marie Skłodowska Curie Action (MSCA) have been to (a) collect and sequence childhood sarcomas (bone and muscle cancers); (b) collect and sequence embryonic and foetal normal reference bone and muscle; and (c) develop and apply new computational tools to understand childhood sarcoma. A parallel goal of the MSCA fellowship was to hone the skills and facilitate the career development of the researcher.
Data: CORDIS, © European Union
Project objective
Each year more than 35,000 European children and young people are diagnosed with cancer. Childhood cancer remains a major public health and socioeconomic issue in Europe and around the world. Cancer arises when a single cell transforms and divides uncontrollably, resulting in a malignant mass of tumour cells. To study cancer, we must understand how these normal cells change. Our current understanding of how normal cells vary across the many tissues of our body is poorly understood. Child development represents a unique challenge in understanding our cells, as children’s bodies change at a cellular level entirely different than adults. This is reflected in the spectrum of cancers diagnosed in children compared to adults, particularly in bone and soft tissue cancers (sarcomas) where they present in less than 1% of adults' cancers and nearly 21% of children's cancers. With the advent of high-throughput single-cell RNA sequencing (scRNA-seq), it is now possible to analyze cell populations at remarkable scale and resolution. The primary purpose of this project is to use scRNA-seq to reconstruct the phylogenetic cellular lineage of childhood and adult sarcomas, and corresponding normal tissue. This fellowship aims to (1) discover and define differences between normal and cancer cell biology at single-cell resolution and (2) use machine learning to determine the cell type (cell-of-origin), the somatic changes and transcriptional trajectories of normal cells that lead to malignant transformation in children compared to adults.This project represents the highest resolution map of the intratumour genetic heterogeneity and clonal evolution of sarcoma ever produced. Another outcome of this project will be a reference map of all of the somatic mutations and expression profiles of normal bone and cartilaginous tissue. This will be a pivotal resource for the global research community - the ‘Bone’ and ‘Cartilage’ branches of the ‘Developmental Human Cell Atlas’.
Original text from CORDIS.
Participants
- GENOME RESEARCH LIMITED LBG · SAFFRON WALDENCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union