DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation. Farlik, M., Halbritter, F., Müller, F., Choudry, F. A., Ebert, P., Klughammer, J., Farrow, S., Santoro, A., Ciaurro, V., Mathur, A., Uppal, R., Stunnenberg, H. G., Ouwehand, W. H., Laurenti, E., Lengauer, T., Frontini, M., & Bock, C. Cell Stem Cell, 19(6):808–822, 12, 2016.
doi abstract bibtex

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.

@article{Farlik.2016, 
year = {2016}, 
rating = {0}, 
title = {{DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation}}, 
author = {Farlik, Matthias and Halbritter, Florian and Müller, Fabian and Choudry, Fizzah A. and Ebert, Peter and Klughammer, Johanna and Farrow, Samantha and Santoro, Antonella and Ciaurro, Valerio and Mathur, Anthony and Uppal, Rakesh and Stunnenberg, Hendrik G. and Ouwehand, Willem H. and Laurenti, Elisa and Lengauer, Thomas and Frontini, Mattia and Bock, Christoph}, 
journal = {Cell Stem Cell}, 
issn = {1934-5909}, 
doi = {10.1016/j.stem.2016.10.019}, 
pmid = {27867036}, 
pmcid = {PMC5145815}, 
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.}}, 
pages = {808--822}, 
number = {6}, 
volume = {19}, 
language = {English}, 
month = {12}
}

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