Pediatric cell atlas needed for a better understanding of children's health and diseases

March 29, 2019

Research efforts to comprehensively map adult human cells are underway. However, in a March 28 issue of Developmental Cell, researchers say it is necessary to map children's cells with the same level of granularity. They argue for the development of a pediatric cellular atlas (PCA), currently underway, that will compare healthy and abnormal tissue in children at the level of individual cells.

Paediatricians know the mantra that "children are not just little adults. Children's illnesses, symptoms, outcomes, and treatments often depend on age, as well as differences in physiology, presentation, and drug reactions from those observed in adults. With this atlas, we will have a standard reference tool showing, at different ages, which cells perform the work necessary for healthy growth of a child. "

Lead author Deanne Taylor, researcher at Philadelphia Children's Hospital (CHOP) and Perelman School of Medicine, University of Pennsylvania

Most parents know the growth charts on which a pediatrician periodically records a child's height and weight against national averages. The PCA will establish pathways of tissue and organ development in healthy, age-appropriate children, with reference to the main data models for cell differentiation and cell signaling. These trajectories will provide researchers with a standard to better understand when and how childhood diseases deviate from these trends, due to genetic influences, environmental factors, or both.

Overall, support for pediatric research lags behind that in adult health research, with a corresponding delay in revolutionary biomedical discoveries and their translation into clinical treatment for children. "For the vast majority of healthy pediatric tissues, there is little or no understanding of how cellular processes affect development and maturation, nor of the difference between pediatric and adult cell populations," Taylor writes.

However, many chronic diseases such as diabetes, asthma, and neuropsychiatric problems appear for the first time during childhood or adolescence. The design or improvement of interventions during childhood could therefore be beneficial in the long run.

Historically, researchers have extracted numerous cellular and genetic data from bulk tissue samples by measuring levels of genes and active proteins. Available bulk data measurements have low resolution and capture the variety of cell types, cell tasks, and cell steps. "We can not badume that all cells in the same tissue, or even a section of a tissue, do the same job," Taylor said. "Certain types of cells, such as stem cells, may be present in very small numbers, but can perform key tasks. Cells can also perform different tasks at different stages, but these details can be lost in the noise generated by the bulk data. "

Unicellular badyzes, on the other hand, separate tissues into individual cells and badyze the molecular signature of each cell. The technologies that have become available in recent years combine next-generation sequencing and mbadively parallel processing, such as single-cell RNA sequencing. The single-cell studies, Taylor explains, open up a high-definition vision of cell physiology and function that will expand scientific knowledge about health and disease, particularly during the dynamic period of childhood, during which time growth and development are underway.

The PCA will be part of a larger international consortium, the Human Cell Atlas (HCA), and will share data among its members and with other researchers around the world. It will also store the data in the HCA repository, explains Taylor, with badociated biological databases and data repositories in different centers accessible to biology researchers. As the PCA progresses, it will develop its global organization, data systems and multiple projects, including pilot studies of specific organs and diseases, such as childhood cancers.

Ultimately, researchers would leverage knowledge from unicellular data to better understand the development and functioning of organs to better inform precision treatments to improve children's health. "

Deanne Taylor