Publication highlights

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Explore a selection of research case studies from the past five years.

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Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

God with two faces

Surprising ‘two-faced’ cancer gene role supports paradigm shift in predicting disease

Loss of the tumour suppressor gene CDKN2A is a common early event in development of the pre-cancerous condition Barrett's oesophagus. Around 1% of Barrett's patients go on to develop oesophageal adenocarcinoma, but rather than enhancing this progression, as would be expected, early CDKN2A loss is actually protective. Having made this striking observation, the team at the Crick and collaborators showed that the reason lies with a second tumour suppressor gene, TP53. Loss of TP53 is a key driver of transformation into oesophageal cancer, but if CDKN2A is also missing, the Barrett's cells are too weakened to progress. CDKN2A changes sides to become a villain later in the process: if it's lost after the cancer has developed, it promotes a more aggressive tumour.

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer

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Published in Nature Cancer

Published

x-ray of a fetal thymus

First 3D images of complete human thymus shine light on its structure and function

Researchers in the Epithelial Stem Cell Biology & Regenerative Medicine Laboratory at the Crick and the Advanced X-Ray Imaging Group at UCL have taken the first 3D images of a whole human thymus. They used ‘phase contrast computed tomography’ (PC-CT) to take detailed 3D images of thymi from developing fetuses or babies aged under one year. The imaging method showed how the ratio of the cortex and the medulla, the two compartments in the thymus, changes with age, and that structures called Hassall's bodies appear early during organ development. Hassall's bodies occupy about a quarter of the thymic medulla in children, suggesting they play a role in immunity. Finally, the team found that a smaller-scale version of the X-ray technique, called edge illumination, could also distinguish between the cortex and the medulla and show Hassall's bodies.

Advanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments

Published in Communications Medicine

Published

Thymus

Researchers identify stem cells in the thymus for the first time

Researchers at the Francis Crick Institute and UCL have identified stem cells in the human thymus for the first time. These cells represent a potential new target to understand immune diseases and cancer and how to boost the immune system. The researchers found that these stem cells, named Polykeratin cells, express a variety of genes allowing them to give rise to many cell types not previously considered to have a common origin. They can develop into epithelial as well as muscle and neuroendocrine cells, highlighting the importance of the thymus in hormonal regulation. The researchers isolated Polykeratin stem cells in a dish and were able to show that thymus stem cells can be extensively expanded. They demonstrated that all the complex cells in the thymus epithelium could be produced from a single stem cell, highlighting a remarkable and yet untapped regenerative potential.

Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus

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Published in Developmental Cell

Published

Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds

In this paper we define the heterogeneity and the clonogenic potential of human thymus stroma; characterise progenitor cells capable of extensive expansion in vitro, thereby achieving clinically relevant numbers with resilience to long-term storage; and report an epithelial-mesenchymal hybrid phenotype of thymus epithelial cells in vivo and in vitro that affects cell behaviour, a unique feature among any epithelia so far reported. We describe a protocol for organs that lack a main vascular access that allowed us to specify the role of natural ECM in supporting organ morphogenesis ex vivo and in vivo; and reconstitute a functional human thymus long-term in vivo.

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Published in Nature Communications

Published

Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure

Children with intestinal failure cannot absorb the nutrients that are essential to be healthy. In the most severe cases, patients may require transplantation. However, there is a shortage of donor organs and complications can arise after surgery. We have shown how intestinal stem cells and intestinal tissues taken from patients can be used to grow functioning intestinal grafts in the laboratory, which could offer a safe and longer-lasting alternative to traditional donor transplants.

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Published in Nature Medicine

Published

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Research case studies 

Explore a selection of recent case studies that spotlight particular areas of research at the Crick.