title: Identification of DNA methylation changes at cis-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing.
abstract: Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important cis-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation.
authors.affiliation: a Division of Epigenomics and Cancer Risk Factors , German Cancer Research Center (DKFZ) ; Heidelberg , Germany.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Lipka
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Nina
authors.initials: N
authors.lastname: Cabezas-Wallscheid
authors.forename: Daniel
authors.initials: D
authors.lastname: Klimmeck
authors.forename: Dieter
authors.initials: D
authors.lastname: Weichenhan
authors.forename: Carl
authors.initials: C
authors.lastname: Herrmann
authors.forename: Amelie
authors.initials: A
authors.lastname: Lier
authors.forename: David
authors.initials: D
authors.lastname: Brocks
authors.forename: Lisa
authors.initials: L
authors.lastname: von Paleske
authors.forename: Simon
authors.initials: S
authors.lastname: Renders
authors.forename: Peer
authors.initials: P
authors.lastname: Wünsche
authors.forename: Petra
authors.initials: P
authors.lastname: Zeisberger
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.forename: Simon
authors.initials: S
authors.lastname: Haas
authors.forename: Marieke Ag
authors.initials: MA
authors.lastname: Essers
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.forename: Michael D
authors.initials: MD
authors.lastname: Milsom
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D016678:Genome; D006412:Hematopoietic Stem Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*
keywords: DNA methylation; differentiation; epigenetics; haematopoietic stem cells; progenitor cells