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Identification and Isolation of Oligopotent and Lineage-committed Myeloid Progenitors from Mouse Bone Marrow
Published on: July 29, 2018
Comprehensive methylome map of lineage commitment from haematopoietic progenitors
Hong Ji1, Lauren I R Ehrlich, Jun Seita
1Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, 570 Rangos, 725 N. Wolfe St., Baltimore, Maryland 21205, USA.
Nature
|August 20, 2010
Summary
DNA methylation patterns change during blood cell development. This study maps these epigenetic changes in hematopoietic progenitors, revealing key genes and pathways involved in myeloid versus lymphoid differentiation.
Area of Science:
- Hematology
- Epigenetics
- Molecular Biology
Background:
- Lineage-specific differentiation relies on epigenetic modifications, as DNA sequences remain unchanged in terminally differentiated cells.
- Hematopoiesis, the process of blood cell formation, serves as a model for studying epigenetic changes during cell-fate decisions.
- While DNA methylation is crucial for myeloid/lymphoid differentiation, a comprehensive DNA methylation map of hematopoietic progenitors is lacking.
Purpose of the Study:
- To create a comprehensive DNA methylation map of various hematopoietic progenitor populations.
- To investigate the relationship between DNA methylation and gene expression during myeloid versus lymphoid differentiation.
- To identify novel genes and pathways involved in hematopoietic lineage commitment.
Main Methods:
- Genome-wide analysis of 4.6 million CpG sites in specific hematopoietic progenitor populations (MPPs, CLPs, CMPs, GMPs, DN1-3).
- Correlation analysis of differential DNA methylation with gene expression patterns.
- Functional assessment using DNA methyltransferase inhibitors to observe lineage skewing.
Main Results:
- Significant epigenetic plasticity was observed during both lymphoid and myeloid restriction.
- Myeloid commitment showed lower global DNA methylation compared to lymphoid commitment.
- Differential DNA methylation correlated with gene expression, particularly at CpG island shores.
- Identification of previously unrecognized genes (e.g., Arl4c, Jdp2) and transcription factors (e.g., Meis1) involved in lineage choice.
- Epigenetic modification of epigenetic regulators themselves was implicated in differentiation.
Conclusions:
- DNA methylation is dynamically modulated during lineage-specific hematopoietic differentiation.
- This study provides a comprehensive map of methylation and transcriptional changes during myeloid versus lymphoid fate decisions.
- Epigenetic mechanisms, including DNA methylation, play a critical role in regulating hematopoietic stem cell differentiation and maintaining cell identity.
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