DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

Publication date: Available online 17 November 2016
Source:Cell Stem Cell
Author(s): Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A. Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G. Stunnenberg, Willem H. Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, Christoph Bock
Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood. We also observed lineage-specific DNA methylation between myeloid and lymphoid progenitors, characterized immature multi-lymphoid progenitors, and detected progressive DNA methylation differences in maturing megakaryocytes. We linked these patterns to gene expression, histone modifications, and chromatin accessibility, and we used machine learning to derive a model of human hematopoietic differentiation directly from DNA methylation data. Our results contribute to a better understanding of human hematopoietic stem cell differentiation and provide a framework for studying blood-linked diseases.

Graphical abstract

Teaser

As part of the IHEC consortium, Bock and colleagues present genome-wide reference maps of DNA methylation dynamics during human blood development. The characteristic DNA methylation patterns they see in the different cell types allow data-driven inference of an epigenome-based model of hematopoietic differentiation. Explore the IHEC web portal at http://ift.tt/2gczkgR.


http://ift.tt/2g4ksxD