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Fresh hope of new cancer and autoimmune disease therapies as Wellcome Sanger Institute creates map of thymus gland



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Hopes of new therapies to treat cancer and autoimmune diseases have been raised after the origins of our immune system were mapped.

Researchers at the Wellcome Sanger Institute in Hinxton, working with colleagues at Newcastle University and Ghent University in Belgium, have created the first cell atlas of the human thymus gland.

Located in the chest, this gland produces T cells - the crucial white blood cells that fight infection and disease.

An illustration of the human thymus (30596118)
An illustration of the human thymus (30596118)

After leaving the thymus, these cells enter the blood and other parts of the body to mature further. They then seek out and destroy invading bacteria and viruses, and are capable of recognising and killing cancer cells.

Sometimes called the ‘pacemaker of life’, the thymus is unusual in that it is largest and most active in childhood and shrinks after puberty, almost disappearing by the age of 35.

Problems in thymus development can lead to defective T cell generation. This can result in severe immune deficiencies such as severe combined immunodeficiency (SCID), which leaves people susceptible to infections, or may affect T cell regulation, which can result in autoimmune diseases such as Type 1 diabetes.

Scientists have a good understanding of mature T cells through previous studies, but the development of the human thymus and T cells within is not fully understood.

The human thymus atlas has uncovered new cell types and identified signals instructing immature immune cells how to develop into T cells.

Ultimately, the information could help researchers to generate an artificial thymus and engineer improved therapeutic T cells.

The work forms of the huge Human Cell Atlas initiative, which will create a kind of ‘Google map’ of the entire human body.

Dr Jongeun Park, the first author on the study from the Wellcome Sanger Institute, said: “We have produced a first human thymus cell atlas to understand what is happening in the healthy thymus across our lifespan, from development to adulthood, and how it provides the ideal environment to support the formation of T cells.

“This openly available resource will allow researchers worldwide to understand how the immune system develops to protect our body.”

Reporting their work in the journal Science, the research team told how they used single cell technology to isolate and analyse around 200,000 individual cells from the developing thymus, along with child and adult thymus tissue.

Exploring which genes were active in each individual cell, they identified new cell types and used those genes as tags, mapping each cell to its exact location in the thymus.

Dr Muzlifa Haniffa, Wellcome Trust Senior Research Fellow in Clinical Science photographed on a Leica TCS SP8 X in the BioImaging Unit, Super Resolution Imaging Lab, Newcastle University. (30596645)
Dr Muzlifa Haniffa, Wellcome Trust Senior Research Fellow in Clinical Science photographed on a Leica TCS SP8 X in the BioImaging Unit, Super Resolution Imaging Lab, Newcastle University. (30596645)

Professor Muzlifah Haniffa, a senior author of the study from Newcastle University and senior clinical fellow at the Wellcome Sanger Institute, said: “With this thymus cell atlas, we are unravelling the cellular signals of the developing thymus, and revealing which genes need to be switched on to convert early immune precursor cells into specific T cells.

“This is really exciting as in the future, this atlas could be used as a reference map to engineer T cells outside the body with exactly the right properties to attack and kill a specific cancer – creating tailored treatments for tumours.”

In the clinic, therapeutic T cells are already being used to treat B-cell lymphoma and leukaemia cancers but creating the right subtype of T cells is problematic.

Professor Tom Taghon, a senior author of the study from Ghent University, Belgium, said: “We now have a very detailed understanding of how T cells form in healthy tissue.

“We have been able to identify a similar population of precursor cells in the developing thymus and liver, and we believe that these precursors are important for initiating T cell development in the foetus, and for the establishment of a fully competent thymus organ.

“This is helping us put jigsaw pieces together to get a bigger picture of how immunity develops.”

Exploring the development of the thymus and how it withers with age could shed new light on ageing and explain how the immune system changes through life.

Dr Sarah Teichmann FMedSci, Cellular Genetics Programme Head, WTSI, in front of the computer cluster at Sanger. Picture: Pari Naderi. (30595950)
Dr Sarah Teichmann FMedSci, Cellular Genetics Programme Head, WTSI, in front of the computer cluster at Sanger. Picture: Pari Naderi. (30595950)

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas organising committee, said: “This map of the thymus is an important part of the Human Cell Atlas mission to chart every cell type in the human body. It is helping us learn about developmental pathways within the body, and the age-associated decline of the immune system. This has applications in cellular engineering, including the possibility of creating an artificial thymus for regenerative medicine.”

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