Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Author:

Saeed Sadia1,Quintin Jessica2,Kerstens Hindrik H. D.1,Rao Nagesha A.1,Aghajanirefah Ali1,Matarese Filomena1,Cheng Shih-Chin2,Ratter Jacqueline2,Berentsen Kim1,van der Ent Martijn A.1,Sharifi Nilofar1,Janssen-Megens Eva M.1,Ter Huurne Menno1,Mandoli Amit1,van Schaik Tom1,Ng Aylwin34,Burden Frances56,Downes Kate56,Frontini Mattia56,Kumar Vinod7,Giamarellos-Bourboulis Evangelos J.8,Ouwehand Willem H.56,van der Meer Jos W. M.2,Joosten Leo A. B.2,Wijmenga Cisca7,Martens Joost H. A.1,Xavier Ramnik J.34,Logie Colin1,Netea Mihai G.2,Stunnenberg Hendrik G.1

Affiliation:

1. Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.

2. Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.

3. Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA.

4. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

5. Department of Haematology, University of Cambridge, Cambridge, UK.

6. National Health Service, Blood and Transplant Cambridge Centre, Cambridge Biomedical Campus, Cambridge CB0 2PT, UK.

7. University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.

8. Fourth Department of Internal Medicine, University of Athens, Medical School, 1 Rimini Street, 12462 Athens, Greece.

Abstract

A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducing immune responses, Saeed et al. document the epigenetic changes in the genome that underlie immune cell differentiation. Cheng et al. demonstrate that trained monocytes are highly dependent on the breakdown of sugars in the presence of oxygen, which allows cells to produce the energy needed to mount an immune response. Chen et al. examine RNA transcripts and find that specific cell lineages use RNA transcripts of different length and composition (isoforms) to form proteins. Together, the studies reveal how epigenetic effects can drive the development of blood cells involved in the immune system. Science , this issue 10.1126/science.1251086 , 10.1126/science.1250684 , 10.1126/science.1251033

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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