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Developmental Biology - Pediatric Cell Atlas

A 'Single Cell' Atlas For Children's Health

A Pediatric Cell Atlas is in planned to map single-cell changes and give deeper understanding of child health and disease...

Biomedical researchers plan to create a Pediatric Cell Atlas (PCA), as a powerful new resource for fine-grained scientific understanding of human growth and development.
Dramatic recent advances in technology, allow an unprecedented window on the unique biology of children. The PCA will benchmark healthy and abnormal tissues at the single cell level.

"Pediatricians are familiar with the mantra that 'children are not just small adults. Children's diseases, symptoms, outcomes and therapies are often age-dependent, along with differences in physiology, presentation and drug responses compared to those occurring in adults. With this Atlas, we'll have a standard reference tool showing, at different ages, which cells are doing the work for a child to grow healthily."

Deanne M. Taylor PhD, Director of Bioinformatics, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia (CHOP); research assistant professor of Pediatrics, the Perelman School of Medicine at the University of Pennsylvania, USA and first author.

Deanne Taylor PhD, is the first and corresponding author of an open-access perspective article on the PCA in the journal Developmental Cell. Her co-first authors are Bruce J. Aronow PhD, Division of Biomedical Informatics at Cincinnati Children's Hospital Medical Center, and CHOP researcher Kai Tan PhD, also of Penn Medicine. Other co-authors represent Boston Children's Hospital, Children's National Medical Center, Beatrix Children's Hospital and the National Institutes of Health, among other institutions. A global coalition of pediatric researchers creating a high-definition view of children's health.

Most parents are familiar with growth charts, on which a pediatrician periodically logs a child's height and weight in comparison to national averages. 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, due to genetic influences, environmental factors or both.
Support for pediatric research lags behind support for adult health research, with a corresponding lag in breakthrough biomedical discovery translated into clinical treatments for children.

While addressing this disparity with its own pediatric research, CHOP also places its work in the broader context of lifespan medicine — identifying progress in health and disease over the fetal-to-adult continuum. Many lifelong chronic diseases, such as diabetes, asthma and neuropsychiatric conditions, first become apparent in childhood or adolescence. Designing or improving interventions in childhood could yield lifelong benefits. The PCA will provide key evidence for advancing such efforts.

Historically, research extracts much cell and genetic data from bulk tissue samples by measuring levels of active genes and proteins. These bulk data measurements are low-resolution in their ability to capture diversity in cell type, tasks and stages. Taylor: "We can't assume that all the cells in one tissue, or even one section of a tissue, are doing the same jobs. Some cell types — such as stem cells — may be present in very low numbers, yet perform key tasks. Cells also perform different tasks at different stages, details lost in the noise of bulk data."
Single-cell analyses separates tissues into individual cells, analyzing each cell's molecular signature. Technology over the past few years can now combine next-generation sequencing with massive parallel processing - as in RNA sequencing of single cells.

Single-cell studies open a high-definition view of cell physiology and function, expanding scientific information on health and disease - particularly during the dynamic period of childhood growth and development.

The PCA will be part of the Human Cell Atlas (HCA) sharing data among members and with other researchers worldwide.

Two of the co-founders of the HCA initiative, Dr. Aviv Regev of the Broad Institute, and Dr. Sarah Teichmann, of the Wellcome Sanger Institute, are co-authors of the current PCA paper.

The PCA will also store data in the HCA repository, explains Taylor, with associated biobanking and data repositories in different centers available to biological research. Moving forward, it will develop overall organization, data systems and multiple projects, including pilot studies by specific organs and disease areas, such as childhood cancers.
"Ultimately, researchers would leverage knowledge from single-cell data into a deeper understanding of organ development and function, to inform precision treatments advancing child health."

Deanne M. Taylor PhD, Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia; Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan.

Deanne M. Taylor, Bruce J. Aronow, Kai Tan, Kathrin Bernt, Nathan Salomonis, Casey S. Greene, Alina Frolova, Sarah E. Henrickson, Andrew Wells, Liming Pei, Jyoti K. Jaiswal, Jeffrey Whitsett, Kathryn E. Hamilton, Sonya A. MacParland, Judith Kelsen, Robert O. Heuckeroth, S. Steven Potter, Laura A. Vella, Natalie A. Terry, Louis R. Ghanem, Benjamin C. Kennedy, Ingo Helbig, Kathleen E. Sullivan, Leslie Castelo-Soccio, Arnold Kreigstein, Florian Herse, Martijn C. Nawijn, Gerard H. Koppelman, Melissa Haendel, Nomi L. Harris, Jo Lynne Rokita, Yuanchao Zhang, Aviv Regev, Orit Rozenblatt-Rosen, Jennifer E. Rood, Timothy L. Tickle, Roser Vento Tormo, Saif Alimohamed, Monkol Lek, Jessica C. Mar, Kathleen M. Loomes, David M. Barrett, Prech Uapinyoying, Alan H. Beggs, Pankaj B. Agrawal, Yi-Wen Chen, Amanda B. Muir, Lana X. Garmire, Scott B. Snapper, Javad Nazarian, Steven H. Seeholzer, Hossein Fazelinia, Larry N. Singh, Robert B. Faryabi, Pichai Raman, Noor Dawany, Hongbo Michael Xie, Batsal Devkota, Sharon J. Diskin, Stewart A. Anderson, Eric F. Rappaport, William Peranteau, Kathryn A. Wikenheiser-Brokamp, Sarah Teichmann, Douglas Wallace, Tao Peng, Yang-yang Ding, Man S. Kim, Yi Xing, Sek Won Kong, Carsten G. Bönnemann, Kenneth D. Mandl and Peter S. White.

The opportunity to contrast children's tissues at a single-cell level across ages would provide a unique and unprecedented window into pediatric diseases and their treatment. The PCA represents a project with challenges in tissue procurement and single-cell preparation but offers significant rewards in the potential contributions to our understanding of children’s health and disease. As a diverse and interdisciplinary effort, the PCA would benefit from programs such as the NIH Common Fund or the recently formed trans-NIH Pediatric Research Consortium (N-PeRC), which was founded to coordinate pediatric research programs across NIH’s 27 institutes and centers. It is expected that some fundraising efforts will often be specific to participating institutions or groups and not PCA-wide, as has been the case across the HCA.

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

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Apr 19 2019   Fetal Timeline   Maternal Timeline   News  

A pediatric single-cell atlas can consist of multi-omics data from hundreds to many thousands of cells isolated from multiple tissues from normally developing and disease-affected individuals. Single cells can be grouped into cell types that have unique molecular profiles representing primary programs for that cell type as well as sub-state-specific additional programming. The utility of a single-cell atlas is the possibility to map molecular signatures driving developmental, physiological, and pathological processes. Thus, single cell-based signatures can reveal the roles and responses of multiple cell lineages that dictate a given organ's and/or tissue's collective biology.

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