AI Article Synopsis

  • Epigenetic changes play a crucial role in guiding and maintaining the lineage commitment of haematopoietic stem cells (HSCs) during blood cell development.
  • The DNA methylation landscape in HSCs is vital for producing mature blood cells, and disruptions in this methylation process can lead to severe blood production issues and contribute to cancer.
  • This article reviews current knowledge about DNA methylation in normal and malignant blood cell formation, highlights new techniques for studying HSC methylation, and presents a dataset from advanced sequencing methods that reveals key regulatory regions involved in early haematopoietic differentiation.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613180PMC
http://dx.doi.org/10.4161/15384101.2014.973334DOI Listing

Publication Analysis

Top Keywords

dna methylation
12
tagmentation-based genome
8
genome bisulfite
8
bisulfite sequencing
8
dna methylome
8
rare cell
8
methylation status
8
status hscs
8
data set
8
methylated cytosines
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!