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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 institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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