Charting Epimutation Dynamics in Human Hematopoietic Differentiation

Overview

Journal Blood Sci

Date 2024 Jun 14

PMID 38872911

Authors

Xiaohuan Qin

Jiayi Lu

Peng Wu

Chunyong Zhang

Lei Shi

Ping Zhu

Affiliations

Soon will be listed here.

Abstract

DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.

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