DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation
| Autor: | 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 |
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| Jazyk: | angličtina |
| Předmět: |
megakaryocyte maturation
cell type prediction bioinformatic lineage reconstruction lymphoid-myeloid lineage commitment DNA methylation profiling single-cell sequencing hematopoietic stem cell differentiation immature lymphoid progenitors reference epigenome mapping whole genome bisulfite sequencing 3. Good health |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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