̽��ֱ�� of Cambridge - Sarah Teichmann

Cartographers of the human body: the Human Cell Atlas

cjb250 — Wed, 20 Nov 2024 16:00:45 +0000

̽��ֱ��Human Cell Atlas is an ambitious project to map every cell in the human body. Its co-lead, Professor Sarah Teichmann, explains how the initiative is already changing our understanding of our bodies.

Immune cell characteristics mapped across multiple tissues

cjb250 — Fri, 13 May 2022 15:41:02 +0000

̽��ֱ��research, from the ̽��ֱ�� of Cambridge, Wellcome Sanger Institute, and collaborators, has created an open-access atlas of the immune cells in the human body and focuses on those found within tissues, which are understudied, compared to those circulating in the blood.

This study is part of the international Human Cell Atlas (HCA) consortium, which is aiming to map every cell type in the human body as a basis for both understanding human health and for diagnosing, monitoring, and treating disease.

Published in Science, the research explores the similarities and differences of the same types of immune cells across 16 different tissues. Knowing more about immune cell traits and reactions in these tissues could help future research into therapies that aim to produce or enhance an immune response to fight disease, such as vaccinations or anti-cancer treatments.

It is one of a trio of milestone collaborative papers published together in Science this week, which have created comprehensive and openly available cross-tissue cell atlases. ̽��ֱ��complementary studies shed light on health and disease, and will contribute towards a single Human Cell Atlas.

̽��ֱ��human immune system is made up of many different types of cells that can be found throughout the body, all playing crucial roles. They not only fight off pathogens when they appear, but remember them so they can be eliminated in the future.

In this new research, scientists simultaneously analysed immune cells across 16 tissues from 12 individual organ donors. ̽��ֱ��team developed a database that automatically classifies different cell types, called CellTypist, to handle the large volume and variation of immune cells. Through this, they were able to identify around 100 distinct cell types.

Using CellTypist and further in-depth analysis, the researchers created a cross-tissue immune cell atlas that revealed the relationship between immune cells in one tissue and their counterparts in others. They found similarities across certain families of immune cells, such as macrophages, as well as differences in others. For example, some memory T cells show unique features depending on which tissue they are in.

̽��ֱ��team also uncovered new insights into immune system memory by sequencing the antigen receptors that are found on T and B cells. This part of the study showed the different states that T and B cells undergo if they are exposed to an antigen, such as those found on bacteria and viruses.

̽��ֱ��wider research community can use this cross-tissue immune cell atlas to help interpret and inform future research. It could also serve as a framework to identify which immune cells could be useful to activate when designing new therapeutics that focus on guiding or supporting the immune system, such as vaccination and immunotherapies, for both infectious diseases and solid tumours.

Dr Cecilia Domínguez Conde, co-first author from the Wellcome Sanger Institute, said: “We have created a novel catalogue of immune cells within the human body, allowing us to automatically identify cell types across multiple tissues. By using single-cell sequencing data we have been able to reveal around a hundred different kinds of immune cells including macrophages, B cells, and T cells, uncovering crucial information about how the immune system works. We would like to thank the donors and their families for making this research possible.”

Dr Joanne Jones, co-senior author from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge, said: “In this research, we not only identified distinct types of immune cells, we also found that certain immune cell types follow specific tissue distribution patterns. Understanding the varying behaviours of the same type of immune cell in multiple areas of the body can help inform research into disease and how treatments that target these cells might impact other tissues.”

Dr Sarah Teichmann from the Wellcome Sanger Institute and the Department of Physics at the ̽��ֱ�� of Cambridge, co-founder of the Human Cell Atlas, said: “Our multi-tissue immune cell atlas is a step towards understanding how the immune system functions throughout the entire body and is an important contribution towards the Human Cell Atlas. In addition to creating a new resource for researchers to classify different cell types, our work will have many translational implications, including serving as a framework for developing therapies to fight immune-related diseases and managing infections.”

Reference
Domínguez Conde. C, Xu. C, Jarvis. LB, Rainbow. DB, Wells. SB, et al. (2022) Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science. DOI: 10.1126/science.abl5197

Adapted from a press release by the Wellcome Sanger Institute

Previously underexplored immune cell populations have been genetically mapped across multiple tissues to provide new insights into how our immune systems work.

Understanding the varying behaviours of the same type of immune cell in multiple areas of the body can help inform research into disease and how treatments that target these cells might impact other tissues

Joanne Jones

Chenqu Suo, Sophie Pritchard, Nadav Yayon (Wellcome Sanger Institute)

Developing immune cells (B cells) from prenatal gut tissue

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Gut research identifies key cellular changes associated with childhood-onset Crohn’s Disease

jg533 — Mon, 07 Dec 2020 16:00:00 +0000

̽��ֱ��results are an important step towards better management and treatment of this devastating condition.

̽��ֱ��research from the ̽��ֱ�� of Cambridge and the Wellcome Sanger Institute is part of the global Human Cell Atlas initiative to map every cell type in the human body. ̽��ֱ��findings reveal intricate cellular mechanisms of how the gut develops.

Crohn’s Disease is a type of Inflammatory Bowel Disease affecting around one in every 650 people in the UK. Incidence has increased dramatically in recent decades, especially in children - who can suffer very aggressive symptoms including abdominal pain, diarrhoea and fatigue. This lifelong condition can have major life implications; the cause is not understood, treatments often don’t work, and there is no cure.

“Crohn’s Disease can be particularly aggressive and more treatment-resistant in children, so there’s a real need to understand the condition when it affects them and perhaps come up with childhood-specific treatments,” said Dr Matthias Zilbauer in the Department of Paediatrics at the ̽��ֱ�� of Cambridge and honorary consultant in paediatric gastroenterology at Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, who led the study.

̽��ֱ��researchers used a cutting-edge technology called single-cell RNA sequencing to look at gene expression in individual cells of the developing human gut, six to ten weeks after conception. They focused on the inner lining of the gut, called the intestinal epithelium, and found that the cells there divide constantly at this early stage, guided by messages from other cell types. This allows the gut to grow and form the structures needed for good gut function later in life.

Tissues from the guts of children with Crohn’s Disease, aged between four and twelve, were also analysed. ̽��ֱ��study revealed that some of the cellular pathways active in the epithelium of the foetal gut appear to be reactivated in Crohn’s Disease. These pathways were not active in healthy children of a similar age. ̽��ֱ��results are published today in the journal Developmental Cell.

“Our results indicate there might be a reprogramming of specific gut cell functions in Crohn’s Disease. We don’t know whether this is the cause of the disease or a consequence of it, but either way it is an exciting step in helping us to better understand the condition,” said Zilbauer.

̽��ֱ��findings shed light on fundamental molecular mechanisms of human gut development. ̽��ֱ��team also found that lab-grown ‘mini-guts’ undergo similar individual cellular changes to those inside a developing foetus. This implies that lab-grown models are a powerful and accurate tool for future research into very early gut development and associated diseases.

“This study is part of the international Human Cell Atlas effort to create a ‘Google map’ of the entire human body. With single-cell RNA sequencing we can look at any tissue and identify the individual cell types it’s made up of, the function of those cells, and even identify new cell types,” said Dr Sarah Teichmann at the Wellcome Sanger Institute, and co-chair of the Human Cell Atlas Organising Committee, whose expertise enabled analysis of the huge amount of data generated by this technique.

She added: “A complex tissue like the gut contains different cell types, and these ‘talk’ to each other - the function of one cell affects the function of another. That’s particularly important in the early stages of gut development, and something we can interrogate using computational analyses of single cell RNA sequencing data.”

While the study focused specifically on the dynamics of intestinal epithelial cells, it generated information on around 90,000 primary human intestinal cells of all types. ̽��ֱ��researchers have made this data openly available at www.gutcellatlas.org, creating a valuable resource for further research and drug discovery targeted at childhood Crohn’s Disease.

“From my own experience we’re diagnosing Crohn’s Disease in younger and younger children, some even under the age of five – it’s very much an emerging disease. It’s a really nasty, lifelong condition, and when children are diagnosed, the whole family is affected,” said Zilbauer.

He added: “We are determined to advance our knowledge in this area, and hopefully improve the lives of these children in the future.”

This research was supported by the Medical Research Council, Wellcome, and the Great Ormond Street Hospital Children’s Charity, Sparks. Addenbrooke’s Hospital in Cambridge is a specialist centre for the investigation and treatment of Inflammatory Bowel Disease in children, serving the east of England.

Reference
Elmentaite, R. & Ross, A. et al: ‘Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease.’ Developmental Cell, December 2020. DOI: 10.1016/j.devcel.2020.11.010

Scientists have tracked the very early stages of human foetal gut development in incredible detail, and found specific cell functions that appear to be reactivated in the gut of children with Crohn’s Disease.

Our results indicate there might be a reprogramming of specific gut cell functions in Crohn’s Disease

Matthias Zilbauer

Kenny Roberts and Sophie Pritchard, Wellcome Sanger Institute

Emerging intestinal villi with stem cells (green) supporting their growth

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̽��ֱ��Royal Society announces election of new Fellows 2020

jg533 — Wed, 29 Apr 2020 17:53:50 +0000

Fellows are chosen for their outstanding contributions to scientific understanding. ̽��ֱ��62 newly elected Fellows embody the global nature of science, and are elected for life through a peer review process based on excellence in science. Past Fellows and Foreign Members include Isaac Newton, Charles Darwin, Dorothy Hodgkin and Stephen Hawking.

̽��ֱ��Royal Society is a self-governing Fellowship made up of the most eminent scientists, engineers and technologists from the UK and the Commonwealth. Its Foreign Members are drawn from the rest of the world. ̽��ֱ��Society’s fundamental purpose is to recognise, promote and support excellence in science and to encourage the development and use of science for the benefit of humanity.

Sir Venki Ramakrishnan, President of the Royal Society, said: “At this time of global crisis, the importance of scientific thinking, and the medicines, technologies and insights it delivers, has never been clearer. Our Fellows and Foreign Members are central to the mission of the Royal Society, to use science for the benefit of humanity.

"While election to the Fellowship is a recognition of exceptional individual contributions to the sciences, it is also a network of expertise that can be drawn on to address issues of societal, and global significance. This year’s Fellows and Foreign Members have helped shape the 21st century through their work at the cutting-edge of fields from human genomics, to climate science and machine learning.

"It gives me great pleasure to celebrate these achievements, and those yet to come, and welcome them into the ranks of the Royal Society.”

̽��ֱ��Cambridge scientists announced today as Royal Society Fellows are:

Professor Kevin Brindle FMedSci, Department of Biochemistry and Cancer Research UK Cambridge Institute. His current research is focused on novel imaging methods for detecting cancer progression and to monitor early tumour responses to treatment, with an emphasis on translating these techniques to the clinic.

Professor Vikram Deshpande, Department of Engineering, for his seminal contributions in microstructural mechanics. His works include developing ‘metallic wood’, sheets of nickel as strong as titanium, but four-times lighter thanks to their plant-like nanoscale pores.

Professor Marian Holness, Department of Earth Sciences. She has created a new approach to decoding rock history, and concentrates on understanding the evolution of bodies of magma trapped in the crust, which ultimately controls the eruptive behaviour of any overlying volcano.

Professor Giles Oldroyd, Russell R Geiger Professor of Crop Science, Crop Science Centre and Group Leader, Sainsbury Laboratory. He is leading an international research programme attempting to achieve more equitable and sustainable agriculture through the enhanced use of beneficial microbial associations.

Professor Hugh Osborn, Department of Applied Mathematics and Theoretical Physics for work in theoretical physics on quantum field theory and in particular conformal field theory.

Professor Didier Queloz, Cavendish Laboratory, for his part in the discovery of the first planet beyond our solar system, for which he shared the Nobel Prize in Physics last year. Hundreds more exoplanets have since been revealed by his pioneering observational techniques.

Dr Sarah Teichmann FMedSci, Director of Research, Cavendish Laboratory and Senior Research Fellow, Churchill College, for her contributions to computational biology and genomics, including her role in founding and leading the Human Cell Atlas international consortium to map all cell types in the human body.

Professor Stephen Young, Department of Engineering, for pioneering the statistical approach to language processing - namely, treating conversation as a reinforcement learning problem - that made the speech-recognition products in millions of homes a reality.

Professor Jack Thorne, Department of Pure Maths and Mathematical Statistics for multiple breakthroughs in diverse areas of algebraic number theory. At age 32, he becomes the youngest living member of the Fellowship.

In addition, Dr William Schafer at the MRC Laboratory of Molecular Biology, based at the Cambridge Biomedical Campus, has been elected as a Fellow.

Nine Cambridge scientists are among the new Fellows announced today by the Royal Society.

At this time of global crisis, the importance of scientific thinking, and the medicines, technologies and insights it delivers, has never been clearer.

Venki Ramakrishnan

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