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Encyclopedia of stem cells – Identification of regulatory networks in hematopoietic stem cells and their immediate progeny

No. 38c4e | 22/08/2014

A network of DNA Repair Genes protects Hematopoietic Stem Cells from DNA damage during the onset of proliferation.

A network of DNA Repair Genes protects Hematopoietic Stem Cells from DNA damage during the onset of proliferation.
© Nina Cabezas/DKFZ

In this study, scientists from the German Cancer Research Center (DKFZ) and the European Molecular Biology Laboratory (EMBL) present integrated quantitative proteome, transcriptome and DNA-methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. The groups headed by Andreas Trumpp, Christoph Plass, Michael Milsom (DKFZ), Jeroen Krijgsveld and Wolfgang Huber (EMBL) participated in this study. By characterization of more than 6,000 proteins, 27,000 transcripts and 15,000 differentially methylated regions (DMRs) they identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of DNA methylation during differentiation, and the overall change in DNA methylation inversely correlates with gene expression at key loci. The data reveal the differential expression landscape of 493 transcription factors and 682 lncRNAs and highlight specific expression clusters operating in HSCs. The authors also found an unexpectedly dynamic pattern of transcript isoform regulation, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells. This study provides a comprehensive genome-wide resource for functional exploration of molecular, cellular and epigenetic regulation at the top of the hematopoietic hierarchy.

Nina Cabezas-Wallscheid, Daniel Klimmeck, Jenny Hansson, Daniel B. Lipka, Alejandro Reyes, Qi Wang, Dieter Weichenhan, Amelie Lier, Lisa von Paleske, Simon Renders, Peer Wünsche, Petra Zeisberger, David Brocks, Lei Gu, Carl Herrmann, Simon Haas, Marieke A. G. Essers, Benedikt Brors, Roland Eils, Wolfgang Huber, Michael D. Milson, Christoph Plass, Jeroen Krijgsveld, and Andreas Trumpp: Identification of Regulatory Networks in HSCs and their Immediate Progeny Via Integrated Proteome, Transcriptome and DNA Methylome Analysis. Cell Stem Cell 2014, 10.1016/j.stem.2014.07.005

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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