Tendons are fibrous tissue that connect muscle to bone and are involved in all forms of movement. They are prone to inflammation and tears; for example, tears of the shoulder tendons affect around half of people aged over 65 years, making tendon disease the third most prevalent cause of musculoskeletal pain.
NDORMS Associate Professor Sarah Snelling, the lead investigator of The Tendon Seed Network says: "For the first time we will be able to explore healthy tendons, determining the identity of the individual cells it contains and mapping their spatial arrangement within tendon's complex structural architecture."
"Tendons are particularly challenging to study as they don't contain many cells but do contain lots of "matrix" – a group of proteins that give tendon its fibrous structure. Thanks to our world-leading team, unique funding from the CZI and recent technological advances in single-cell RNA sequencing, we are finally in a position to uncover some of tendon's mysteries at an unprecedented resolution."
The multidisciplinary Tendon Seed Network team based at the University of Oxford, ETH Zurich, University of Copenhagen and University of Glasgow will develop and integrate single-cell sequencing workflows using clinical, biological, computational and mathematical expertise and tools. These tools will be applicable to other hard-to-reach and hard-to-process tissues like cartilage and bone.
Dr Adam Cribbs, also of NDORMS and responsible for leading the computational element of the project, says: "The development of ground-breaking computational tools and mathematic models will be key to delivering our project goals. These open-source tools developed in Oxford will be shared across the Tendon Seed Network, Human Cell Atlas and wider research community. They will allow us to investigate how the spatial and cellular diversity of tendon is influenced by the interplay between tendon type, single-cell identities and matrix composition."
The exploration of healthy human tendon is also enabled through the large clinical component of the project, led by Senior Orthopaedic surgeon and researcher Dr Steve Gwilym and by Dr Mathew Baldwin. "The clinical possibilities of this work are extremely exciting. A cellular blueprint of normal tendon will provide us with a quantifiable benchmark of disease response - allowing us to better evaluate treatments that aim to return tendons to a healthy state" says Dr Gwilym.
Dr Baldwin adds: "We will also further improve our minimally invasive tendon biopsy technique, making personalised treatment and response-assessment increasingly likely on a large scale. Determining the minimum size biopsy amenable to single cell sequencing approaches is translatable to the many hard-to-reach tissues that will comprise the Human Cell Atlas"
CZI is supporting the Human Cell Atlas with $68 million in funding through their newly launched Seed Networks. The Tendon Seed Network is one of 38 collaborative science teams supported by CZI, as part of their commitment to the Human Cell Atlas.
These collaborative groups bring together scientists, computational biologists, software engineers, and physicians to support the continued development of the Human Cell Atlas (HCA), an international effort to map all cells in the human body.
Participants in the three-year Seed Networks projects will focus on mapping specific tissues, such as the heart, eye, or liver, in the healthy human body. The resulting cellular and molecular maps will be a resource for understanding what goes wrong when disease strikes. The Seed Networks grantees represent 20 countries and more than 200 labs, with 45 percent of projects featuring international collaborations.
"The global Human Cell Atlas effort is a beacon for what can be accomplished when experts across scientific fields and time zones work together towards a common goal," said CZI Head of Science Cori Bargmann. "With CZI's Seed Networks grants, we're excited to further support and build interdisciplinary collaborations that will accelerate progress towards a first draft of the Human Cell Atlas."
Founded by Dr. Priscilla Chan and Mark Zuckerberg in 2015, CZI is a new kind of philanthropy that's leveraging technology to help solve some of the world's toughest challenges — from eradicating disease, to improving education, to reforming the criminal justice system. CZI's work in science supports the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of this century.