Epigenomic Profiling of Human CD4(+) T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Durek, P., Nordstroem, K., Gasparoni, G., Salhab, A., Kressler, C., De Almeida, M., Bassler, K., Ulas, T., Schmidt, F., Xiong, J., Glazar, P., Klironomos, F., Sinha, A., Kinkley, S., Yang, X., Arrigoni, L., Amirabad, A. D., Ardakani, F. B., Feuerbach, L., Gorka, O., Ebert, P., Mueller, F., Li, N., Frischbutter, S., Schlickeiser, S., Cendon, C., Froehler, S., Felder, B., Gasparoni, N., Imbusch, C. D., Hutter, B., Zipprich, G., Tauchmann, Y., Reinke, S., Wassilew, G., Hoffmann, U., Richter, A. S., Sieverling, L., Chang, H. D., Syrbe, U., Kalus, U., Eils, J., Brors, B., Manke, T., Ruland, J., Lengauer, T., Rajewsky, N., Chen, W., Dong, J., Sawitzki, B., Chung, H. R., Rosenstiel, Philip, Schulz, M. H., Schultze, J. L., Radbruch, A., Walter, J., Hamann, A., Polansky, J. K. and Deep, Consortium (2016) Epigenomic Profiling of Human CD4(+) T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development Immunity, 45 (5). pp. 1148-1161. DOI 10.1016/j.immuni.2016.10.022.

Full text not available from this repository.

Supplementary data:

Abstract

The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA(+) CD4(+) Tmem cells from blood and CD69(+) Tmem cells from bone marrow (BMTmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptomesupported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmembranched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators.

Document Type: Article
Additional Information: Times Cited: 0 Durek, Pawel Nordstroem, Karl Gasparoni, Gilles Salhab, Abdulrahman Kressler, Christopher De Almeida, Melanie Bassler, Kevin Ulas, Thomas Schmidt, Florian Xiong, Jieyi Glazar, Petar Klironomos, Filippos Sinha, Anupam Kinkley, Sarah Yang, Xinyi Arrigoni, Laura Amirabad, Azim Dehghani Ardakani, Fatemeh Behjati Feuerbach, Lars Gorka, Oliver Ebert, Peter Mueller, Fabian Li, Na Frischbutter, Stefan Schlickeiser, Stephan Cendon, Carla Froehler, Sebastian Felder, Baerbel Gasparoni, Nina Imbusch, Charles D. Hutter, Barbara Zipprich, Gideon Tauchmann, Yvonne Reinke, Simon Wassilew, Georgi Hoffmann, Ute Richter, Andreas S. Sieverling, Lina Chang, Hyun-Dong Syrbe, Uta Kalus, Ulrich Eils, Juergen Brors, Benedikt Manke, Thomas Ruland, Juergen Lengauer, Thomas Rajewsky, Nikolaus Chen, Wei Dong, Jun Sawitzki, Birgit Chung, Ho-Ryun Rosenstiel, Philip Schulz, Marcel H. Schultze, Joachim L. Radbruch, Andreas Walter, Joern Hamann, Alf Polansky, Julia K.
Research affiliation: Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
DOI etc.: 10.1016/j.immuni.2016.10.022
ISSN: 1074-7613
Projects: Future Ocean
Date Deposited: 27 Feb 2017 09:32
Last Modified: 19 Dec 2017 12:45
URI: http://eprints.uni-kiel.de/id/eprint/36065

Actions (login required)

View Item View Item