New paper in Cell Stem Cell as part of the IHEC/BLUEPRINT collection of epigenome mapping studies

This paper uses low-input and single-cell DNA methylation sequencing assays in combination with bioinformatic methods in order to establish genome-wide maps of the epigenome dynamics underlying human hematopoietic stem cell differentiation. A machine learning method was developed and applied for data-driven reconstruction of the human hematopoietic lineage. The paper is part of a collection of papers published by International Human Epigenome Consortium and the BLUEPRINT project

Farlik M*, Halbritter F*, Müller F*, Choudry FA, Ebert P, Klughammer J, Farrow S, Santoro A, Ciaurro V, Mathur A, Uppal R, Stunnenberg HG, Ouwehand WH, Laurenti E, Lengauer T, Frontini M#, Bock C# (2016). DNA methylation dynamics of human hematopoietic stem cell differentiation. Cell Stem Cell, DOI: 10.1016/j.stem.2016.10.019.
*shared first author   # shared corresponding author

Abstract: 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. 

 Epigenetic Landscape of the Blood

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