Three-dimensional genome reorganization in hematopoietic stem cells

Hematopoietic stem cells (HSCs) possess unique characteristics that distinguish them from other hematopoietic progenitor cells, including self-renewal capacity, multipotency, stress response, metabolism, and deep quiescence. Recent advances have significantly enhanced our understanding of the epigenomic states that define these properties. HSCs undergo profound changes in their three-dimensional (3D) genome reorganization throughout development, differentiation, and responses to stimuli. Recent advancements in chromatin conformation capture techniques that require only a small number of cells have provided detailed insights into these dynamic processes. This review explored the latest discoveries in the 3D genome reorganization in HSCs, with a focus on chromatin remodeling during key transitions, including fetal-to-adult development, quiescence-to-activation, differentiation, and aging. We discussed the roles of key transcription factors, epigenetic modifiers, and structural proteins in shaping the 3D genome landscape. Additionally, we examined how alterations in the 3D genome organization impact HSC function and dysfunction in hematologic disorders. Finally, we highlighted future directions in this rapidly evolving field, emphasizing the potential implications of 3D genome research for targeted therapies in hematology.