Boston Children’s ramps up single-cell discovery as a powerful lens on disease

$10M grant will support collaborations across the hospital to create a curated pediatric ‘cell atlas’ to identify disease origins and effective treatments

What happens to our cells during development and disease? How do treatments — current and future — affect our different cell types? Aided by a $10 million gift from the Manton Foundation, Boston Children’s Hospital is investing in a new Cell Discovery Network that will build communities of biologists, computational experts, and clinicians to explore these questions, working closely with patients and their families.

“The goal is to figure out ‘who’ the cells are in a tissue, what they’re doing, and the conversations they’re having with each other,” says José Ordovás Montañés, PhD, an assistant professor in the Division of Gastroenterology, Hepatology, and Nutrition who is co-leading the project with Christopher Walsh, MD, PhD, chief of the Division of Genetics and Genomics. “We then want to see how that changes with disease, particularly diseases that have been under-funded.”

The Manton gift will be used to advance comprehensive studies at the single-cell level across the hospital to enable understanding of the earliest cellular features of normal development and how different cell types behave during health or illness. Such studies include:

  • single-cell RNA sequencing to see what genes different cell types are turning on or off in disease (and even before a clear disease diagnosis);
  • “clonality” studies to capture the dynamics of different populations of cells and identify how DNA mutations impact cells’ function in tissues such as the brain;
  • spatial transcriptomic analyses to understand how different cell types are arranged into “neighborhoods” within tissues; and
  • computational biology to integrate data across studies and link cellular data with clinical knowledge.

“Science has taught us a lot about how individual cells work, but we know much less about how the trillions of cells in our bodies are programmed to come together to create and sustain a whole human body,” says Nancy Andrews, MD, PhD, Executive Vice President and Chief Scientific Officer at Boston Children’s Hospital. “This is a bold and ambitious collaborative effort bringing together biologists, clinicians, and data science experts to bridge that gap in understanding, both in health and in disease.”

Computational biology at the forefront

The core mission of the Cell Discovery Network is to recruit a cohort of computational biologists to teach, enable, and share single-cell science across the hospital, using a common language and working closely with leadership teams. The Network will also provide pilot grants to research labs, especially those focused on difficult-to-treat or poorly defined diseases.

Examples of single-cell studies led by Boston Children’s researchers include:

  • studies of the brain and heart, showing mutations accumulate in cells over time and may contribute to disease
  • studies to understand the cellular dynamics of cancer and other diseases by tracking the development and expansion of rogue cell populations
  • studies of how different kinds of blood cells develop
  • studies of how cancer cells can morph and acquire different properties, making them harder to target
  • studies of how different cell populations in the nose respond when exposed to SARS-CoV-2
  • spatial studies to understand the accumulation of different types of immune cells in autoimmune diseases like lupus.

The power of children’s cells

The larger, long-term goal of the Cell Discovery Network is to develop a comprehensive children’s cell “atlas,” an open resource for examining the earliest origins of disease. Working together with young patients and their families, researchers will seek to identify the “footprints” and triggers of disease and intervene very early in the disease process, before it becomes more chronic and pervasive.

“We’re learning that biological perturbations that cause disease in adults often start very early in life,” says Andrews. “That means that single-cell studies in children may have profound implications for predicting, treating, and ultimately preventing diseases that would manifest decades later.”

Source Boston Children’s Hospital

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