Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis - PubMed (original) (raw)
. 2014 Oct 2;15(4):507-522.
doi: 10.1016/j.stem.2014.07.005. Epub 2014 Aug 21.
Daniel Klimmeck 2, Jenny Hansson 3, Daniel B Lipka 4, Alejandro Reyes 3, Qi Wang 5, Dieter Weichenhan 4, Amelie Lier 6, Lisa von Paleske 1, Simon Renders 1, Peer Wünsche 1, Petra Zeisberger 1, David Brocks 4, Lei Gu 7, Carl Herrmann 5, Simon Haas 8, Marieke A G Essers 8, Benedikt Brors 9, Roland Eils 9, Wolfgang Huber 3, Michael D Milsom 6, Christoph Plass 10, Jeroen Krijgsveld 3, Andreas Trumpp 11
Affiliations
- PMID: 25158935
- DOI: 10.1016/j.stem.2014.07.005
Free article
Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis
Nina Cabezas-Wallscheid et al. Cell Stem Cell. 2014.
Free article
Abstract
In this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of methylation during differentiation, and the overall change in DNA methylation correlates inversely with gene expression at key loci. Our data reveal the differential expression landscape of 493 transcription factors and 682 lncRNAs and highlight specific expression clusters operating in HSCs. We 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 the functional exploration of molecular, cellular, and epigenetic regulation at the top of the hematopoietic hierarchy.
Copyright © 2014 Elsevier Inc. All rights reserved.
Comment in
- Deep diving in the blood stem cell-ome.
Kalaitzidis D, Scadden DT. Kalaitzidis D, et al. EMBO J. 2014 Oct 16;33(20):2281-2. doi: 10.15252/embj.201489778. Epub 2014 Sep 4. EMBO J. 2014. PMID: 25190519 Free PMC article.
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