BLUEPRINT: new perspectives on white blood cells

26 September 2014 – The BLUEPRINT project (www.blueprint-epigenome.eu) to understand human white blood cells has shared its first findings in three papers published in Science. Their initial findings shed light on how the immune system keeps infection at bay, and have implications for advances in transplantation and regenerative medicine. The data are freely available through the European Bioinformatics Institute (EMBL-EBI).

If each of our cells contains a copy of the same genome, what makes one cell differentiate into a blood cell, and another into a liver cell? Part of the answer has to do with influences outside the genome, and part lies in the way DNA is packaged in chromosomes. Epigenetics seeks to understand what makes different DNA elements turn on or off by unwrapping this packaging. Findings in this new area bring science closer to having a ‘master plan’ for each type of cell.

BLUEPRINT is a major initiative to decipher the epigenomes of more than 100 different types of blood cells, including white cells that are crucial to the functioning of the immune system. A project of this scale generates a lot of data, and EMBL-EBI is at the heart of its management, analysis and distribution.

A freely available resource

BLUEPRINT researchers have produced the first freely available, comprehensive catalogue of proteins that regulate processes that give rise to different types of blood cells. These data form the basis for new discoveries, and open up new opportunities for further research.

“The data produced in BLUEPRINT are highly relevant for research into real-time physiological responses, for example the production of macrophages in response to infection,” says Paul Flicek, Head of Vertebrate Genomics at EMBL-EBI. “What makes it so interesting is that it represents specific tissues from real individuals, rather than the cell lines we often work with.”

BLUEPRINT results comprise high-quality raw data, consistently identified epigenetically important regions on the genome and consistent characterisations of genome function. Thanks to meticulous management, the datasets are available from several public resources including the European Genome-phenome Archive, the Blueprint data portal and Ensembl.

“This new and freely available catalogue of RNA molecules in blood progenitor cells provides a rich resource for researchers worldwide,” commented Dr Nicole Soranzo of the Sanger Institute. “It will be of great value in studies that aim to manipulate blood stem cells and their progeny, and is important for future developments in stem cell transplantation therapy, as well as for efforts in regenerative medicine.”

“We have had a surprising number of requests for the datasets already, ahead of publication time,” says Laura Clarke, Coordinator of Resequencing Informatics at EMBL-EBI. “These requests are coming from researchers throughout the world, who are working in either academic or industry settings. We anticipate seeing more and more requests on these rich and very relevant datasets.”

About today’s research

White blood cells called monocytes seek out and infiltrate infected tissue in the body; when they arrive on the scene, they transform into macrophages and destroy the invading pathogen. These ‘innate’ immune cells act quickly and decisively, compared with other immune cells. The level of monocyte activity and macrophage differentiation differ depending of the type of pathogen and infection. During sepsis, for example, these cells reduce their activity for periods of time, when they are considered to be more ‘tolerant’ of the invader, making the person more vulnerable. In contrast, after vaccinations these cells react more strongly to pathogens in a process called ‘trained immunity’.

One of the BLUEPRINT studies published today demonstrates that distinct epigenetic programs kick off immune tolerance or trained immunity. Another shows that cells undergoing trained immunity switch their internal metabolism to glycolysis – a shortcut to increase energy production – to ensure they have the energy they need to fight against pathogens.

The BLUEPRINT achievements are of significant value to the International Human Epigenome Consortium (www.IHEC-epigenomes.org), which aims to find out how the epigenome has shaped human populations over generations and in response to the environment.  

About BLUEPRINT

Supported with €30 million from the European Commission, the BLUEPRINT high-impact project combines the efforts of 41 European universities, research institutes and industry partners to decipher the epigenomes of more than 100 different types of blood cells, including white cells that are crucial to the functioning of the immune system.  The cells are from healthy individuals and of their malignant leukaemic counterparts. In the first stage of the project, reference epigenomes for some of the most abundant white cells in venous blood, cord blood and bone marrow have been established and released. Information about BLUEPRINT data release is available on the project website.

More information about the BLUEPRINT research results are available from the Wellcome Trust Sanger Institute and Radboud University.

Source articles

Saeed, S., et al. (2014) Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science (in press); DOI: 10.1126/science.1251086

Cheng, S-C., et al. (2014) mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity. Science (in press); DOI: 10.1126/science.1250684

Chen, L., et al. (2014) Transcriptional diversity during lineage commitment of human blood progenitors. Science (in press); DOI: 10.1126/science.1251033