Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis

Item Type:	Article
Title:	Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis
Creators Name:	Cabezas-Wallscheid, N. and Klimmeck, D. and Hansson, J. and Lipka, D.B. and Reyes, A. and Wang, Q. and Weichenhan, D. and Lier, A. and von Paleske, L. and Renders, S. and Wünsche, P. and Zeisberger, P. and Brocks, D. and Gu, L. and Herrmann, C. and Haas, S. and Essers, M.A.G. and Brors, B. and Eils, R. and Huber, W. and Milsom, M.D. and Plass, C. and Krijgsveld, J. and Trumpp, A.
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.
Keywords:	Cell Differentiation, Cell Lineage, Cluster Analysis, DNA Methylation, Gene Expression Profiling, Gene Regulatory Networks, Genetic Epigenesis, Genomic Imprinting, Hematopoietic Stem Cells, Human Genome, Long Noncoding RNA, Molecular Sequence Data, Protein Isoforms, Proteome, Transcription Factors, Transcriptome
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Cell Press
Volume:	15
Number:	4
Page Range:	507-522
Date:	2 October 2014
Official Publication:	https://doi.org/10.1016/j.stem.2014.07.005
PubMed:	View item in PubMed

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