Two cutting-edge, cooperative biomedical research projects — the Center for Pediatric Tumor Cell Atlas and the Pediatric Cell Atlas (PCA) — are exploring the potential of single cell technology to zero in on pathogenesis of cancer and other diseases.
Novel technologies have become available in recent years that combine next-generation sequencing and massively parallel processing, such as RNA sequencing, of single cells. These single cell studies, said Deanne Taylor, PhD, director of Bioinformatics in the Department of Biomedical and Health Informatics at Children’s Hospital of Philadelphia and a research assistant professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania, open up a high-definition view of cell physiology and functioning that will expand scientific knowledge of health and disease — particularly during the dynamic childhood period, when growth and development are underway.
The PCA will compile age-matched trajectories of tissue and organ development in healthy children, referencing key data patterns in cell differentiation and cell signaling. Those trajectories will offer a standard for researchers to better understand when and how childhood illnesses diverge from those patterns, because of genetic influences, environmental factors, or both. Enabled by dramatic advances in single-cell technology, the PCA will offer an unprecedented window into the unique biology of children by benchmarking healthy and abnormal tissues at the molecular level.
“Ultimately, researchers would leverage knowledge from single-cell data into a deeper understanding of organ development and function, to better inform precision treatments to advance children’s health,” said Dr. Taylor, who is co-author of an open-access perspective article on the PCA in the journal Developmental Cell.
The PCA is a cornerstone of the Human Cell Atlas (HCA), a global effort into understanding human single-cell biology. As part of the broader international consortium represented in the HCA, the PCA will share data among members and with other researchers worldwide. It will also store data in the HCA’s repository with associated biobanking and data repositories in different centers available to biological researchers. As the PCA moves forward, it will develop its overall organization, protocols, data systems, and multiple projects, including pilot studies of specific organs and diseases.
In addition, the PCA will compare atlas data from healthy tissues with data from diseased tissue, such as those generated by the Center for Pediatric Tumor Atlas. Awarded a five-year research grant totaling $12.5 million, Kai Tan, PhD, an investigator in the Center for Childhood Cancer Research (CCCR) at CHOP, and co-principal investigator Stephen Hunger, MD, chief of the Division of Oncology and director of the CCCR, created the Center as part of a 10-center national consortium.
Drs. Tan and Hunger will work closely with other key investigators in the CCCR at CHOP including Kristina Cole, MD, PhD; Kathrin Bernt, MD; David Barrett, MD, PhD; John Maris, MD; Kristopher Bosse, MD; and Sharon Diskin, PhD. Additional off-site key investigators are Hao Wu, PhD, assistant professor of genetics, and Nancy Zhang, associate professor of statistics, both at University of Pennsylvania, and Kun Zhang, PhD, professor of bioengineering at University of California at San Diego.
Their project is under the umbrella of the larger Moonshot Human Tumor Atlas Network (HTAN) that aims to generate atlases of a diverse cancer patient population and high-risk cancers. The CHOP team is the only pediatric cancer group recipient on account of its world-class pediatric cancer researchers, large volume of patients, and unique ability to acquire biosamples of pediatric cancer.
HTAN will generate a large volume of genomic data, imaging data, and clinical data with a three-pronged goal: an easily searchable, publicly available database; research community access to the computational tools utilized in the project; and access to biospecimens including tissue sections, viably frozen specimens, and patient-derived xenograft models.
“I’m very excited about the kind of promise that can deliver, and that excitement is shared by all the researchers,” Dr. Tan said. “Single cell technologies is revolutionizing biomedical research, not only cancer but other diseases as well.”