Details

Autor(en) / Beteiligte

• Farlik, Matthias
• Halbritter, Florian
• Müller, Fabian
• Choudry, Fizzah A.
• Ebert, Peter
• Klughammer, Johanna
• Farrow, Samantha
• Santoro, Antonella
• Ciaurro, Valerio
• Mathur, Anthony
• Uppal, Rakesh
• Stunnenberg, Hendrik G.
• Ouwehand, Willem H.
• Laurenti, Elisa
• Lengauer, Thomas
• Frontini, Mattia
• Bock, Christoph

Titel

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

Ist Teil von

• Cell stem cell, 2016-12, Vol.19 (6), p.808-822

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Sequencing provides DNA methylation maps of hematopoietic stem and progenitor cells•Methylation differs in HSCs from fetal liver, bone marrow, cord, and peripheral blood•Myeloid and lymphoid progenitors are distinguished by enhancer-linked DNA methylation•Machine learning enables data-driven reconstruction of the hematopoietic lineage 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://www.cell.com/consortium/IHEC.